Best Knee Arthritis Injections Ranked: PRP, Cortisone, Hyaluronic Acid, and Stem Cells | Dr. Jeffrey Peng MD

Medically reviewed by Dr. Jeffrey Peng, MD — Board-Certified Sports Medicine Physician

If you have been diagnosed with knee osteoarthritis, chances are you have heard about injection therapy — but knowing which option is actually worth your time and money can be overwhelming. Corticosteroids, hyaluronic acid, platelet-rich plasma, stem cells — they all promise to help, but the evidence behind each one varies dramatically.

As a sports medicine physician who has treated thousands of patients with knee arthritis, I am going to break down every major injection option and rank them based on the latest clinical evidence, safety data, and what I see working in my practice every day.

Corticosteroid (Cortisone) Injections for Knee Arthritis — C Tier

Steroid injections have been a mainstay of knee arthritis treatment for nearly 70 years. They are inexpensive, quick to administer, and provide fast pain relief — typically lasting about two to three months. For patients dealing with severe knee pain, that short-term benefit can make a meaningful difference.

However, the major concern with cortisone shots is what happens inside the joint over time. A landmark randomized controlled trial published in JAMA found that patients who received corticosteroid injections every three months for two years experienced significantly greater cartilage volume loss compared to those who received saline — with no meaningful difference in pain relief (McAlindon et al., 2017). Additional studies have shown that repeated steroid injections can weaken knee structures and accelerate arthritis progression, ultimately increasing the likelihood of needing knee replacement surgery.

Corticosteroids also carry systemic side effects, including temporary blood sugar elevation and blood pressure increases lasting several days after injection.

This is why cortisone falls in the C tier. That does not mean there is never a role for it. If a patient is about to take a once-in-a-lifetime vacation or attend a family event and their knee suddenly flares up, a cortisone injection is the fastest way to get relief. But once the event passes and the steroid wears off, transitioning to better long-term options that do not carry these risks is essential.

Hyaluronic Acid (Viscosupplementation) Injections for Knee Arthritis — B Tier

Hyaluronic acid — sometimes called viscosupplementation or "gel shots" — is a naturally occurring component of the synovial fluid in our joints. It helps lubricate the joint surfaces, reduce friction, and provide both pain-relieving and anti-inflammatory effects. In knee arthritis, the body produces less hyaluronic acid over time, so the concept behind this treatment is to restore some of that lost cushioning.

A 2025 Bayesian network meta-analysis published in Frontiers in Medicine evaluated ultrasound-guided injections for early-to-mid-stage knee osteoarthritis and ranked hyaluronic acid as the second most effective option overall for improving pain and symptoms, behind PRP (Zhang et al., 2025). The overall response rate for hyaluronic acid is approximately 60 to 70 percent — good, but not exceptional.

The safety profile of hyaluronic acid is excellent, with very few side effects. The main issue to be aware of is a post-injection flare, which occurs in roughly five percent of patients. This reaction causes increased pain and swelling for a few days but resolves on its own and is not dangerous.

Hyaluronic acid earns a B tier ranking. The benefits generally last around six months, and it is covered by Medicare and most private insurance plans, including PPOs and HMOs. While the effectiveness is not as high as PRP, if your insurance covers it, hyaluronic acid is absolutely worth considering — especially if you fall into the 60 to 70 percent of patients who respond well.

PRP (Platelet-Rich Plasma) Injections for Knee Arthritis — S Tier

Platelet-rich plasma has been used for knee arthritis for approximately 15 years, and while it is sometimes called a "newer" treatment, the body of evidence supporting it is now extensive. The most recent clinical trials — including the 2025 network meta-analysis — consistently rank PRP as the best injection available for treating knee osteoarthritis (Zhang et al., 2025).

How PRP Works

The process is straightforward. A small sample of blood is drawn, spun down in a centrifuge to isolate the platelets and growth factors, and then injected directly into the knee under ultrasound guidance. The entire procedure takes about an hour and is performed entirely in the office. PRP delivers a high concentration of growth factors that reduce inflammation, decrease pain, and improve function.

What the Evidence Shows for PRP

Compared to hyaluronic acid, PRP demonstrates a significantly larger effect size — meaning patients who receive PRP tend to experience substantially greater pain relief and functional improvement. A 2025 ESSKA meta-analysis examining over 76,000 patients also found that PRP had the lowest total adverse event rate of all injection options, including corticosteroids and hyaluronic acid (Bensa et al., 2025).

Research has also shown that PRP may slow arthritis progression and reduce the need for knee replacement surgery. A retrospective survival analysis found that 85.7 percent of patients who received PRP did not undergo total knee arthroplasty during a five-year follow-up period, with a median delay to surgery of 5.3 years in those who eventually did require replacement (Sánchez et al., 2020).

In my practice, PRP helps approximately 80 to 90 percent of patients, including many with more advanced disease. That said, like most treatments, it works best in those with mild to moderate arthritis. The main drawback is cost — PRP is not covered by most insurance plans and is typically a self-pay procedure. However, it is one of the most natural treatments available because it uses your own blood with nothing added to it.

Because PRP offers the greatest improvement in pain and function, carries the lowest adverse event profile, and may even protect cartilage and delay or prevent surgery, it earns the S tier ranking. It is, in my opinion, the single best nonsurgical treatment currently available for knee arthritis.

Stem Cell Injections for Knee Arthritis — F Tier

Stem cell therapy is one of the most misunderstood treatments in orthopedics. In the United States, there are only two types of stem cell procedures legally available: bone marrow-derived cells harvested from the pelvic bone (BMAC), and adipose-derived cells obtained from abdominal fat (MFAT).

The first critical point to understand is that these treatments are often marketed as "stem cell injections," but research shows the actual stem cell content is extremely low — usually around one percent. Approximately 99 percent of what is injected is not stem cells. What these preparations do contain are growth factors similar to those found in PRP, but not necessarily in higher concentrations or with better efficacy.

Multiple head-to-head trials comparing bone marrow-derived and adipose-derived injections to PRP have consistently shown the same result: these procedures do not outperform PRP. Yet they are significantly more invasive to harvest and dramatically more expensive.

The theoretical ideal of stem cell therapy — harvesting cells, expanding them in a laboratory, and reinjecting them at therapeutic doses — is not legal in the United States. Patients who travel abroad for expanded stem cell procedures often return with serious complications, including infections and other adverse outcomes.

As it currently stands, stem cell treatment does not have sufficient high-quality evidence to justify its cost, invasiveness, or risks compared to PRP. That is why it falls firmly in the F tier.

Building a Comprehensive Knee Arthritis Treatment Plan

It is important to recognize that injections are only one component of a truly multimodal approach to managing knee arthritis. Exercise and rehabilitation, weight management, nutrition, and other nonsurgical strategies all play critical roles in how your knee feels and functions over time. The most effective outcomes I see in practice come from patients who combine the right injection therapy with a well-rounded treatment plan that addresses the condition from multiple angles.

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Schedule a Consultation

If you are living with knee arthritis and want to explore which injection option is right for you, schedule an evaluation with Dr. Peng. As a board-certified sports medicine physician and published PRP researcher specializing in ultrasound-guided procedures, Dr. Peng can help you understand your options and develop a personalized treatment plan.

Dr. Jeffrey Peng, MD is a Stanford-trained, board-certified sports medicine physician practicing in Campbell, California (San Francisco Bay Area). He specializes in orthobiologics and ultrasound-guided minimally invasive procedures for musculoskeletal conditions.