There is no single “best” injection for knee pain. The right choice depends on how severe your arthritis is, how long you need relief, and whether you’ve already tried other options. Corticosteroid injections remain the most common first-line treatment for quick relief, while hyaluronic acid injections tend to offer longer-lasting benefits for mild-to-moderate osteoarthritis. Platelet-rich plasma (PRP) shows modest short-term gains, and stem cell injections are not FDA-approved for knee pain despite widespread marketing.
Here’s what the evidence actually shows for each type, so you can have a more informed conversation with your doctor about which one fits your situation.
Corticosteroid Injections: Fast but Temporary
Corticosteroid shots are the workhorse of knee pain management. They contain a synthetic version of cortisol that dials down your immune system’s activity at the injection site, which reduces swelling and pain. Most people feel improvement within a few days, and relief typically lasts somewhere between a few weeks and a few months.
The trade-off is that corticosteroids don’t address the underlying problem. They quiet inflammation, but once the drug wears off, the pain returns. More importantly, repeated use may actually make things worse. A two-year clinical trial found that patients who received regular corticosteroid injections lost more cartilage volume than patients who received saline injections, with no meaningful difference in pain between the two groups over that period. That’s a significant finding: the injections may accelerate the joint damage they’re meant to manage.
For this reason, most providers limit corticosteroid injections to a few times per year and use them primarily for flare-ups rather than ongoing maintenance.
Hyaluronic Acid: Slower Onset, Longer Relief
Hyaluronic acid (HA) injections, sometimes called viscosupplementation, work differently. Your knee joint naturally contains hyaluronic acid as part of the fluid that lubricates and cushions the cartilage. In osteoarthritis, that fluid breaks down. HA injections replenish it, improving the joint’s ability to absorb shock and move smoothly.
The results take longer to kick in compared to corticosteroids, often a few weeks, but the benefits tend to last considerably longer. In one long-term study, over 80% of patients receiving HA injections achieved meaningful improvement at 9 to 12 months, compared to less than 10% of patients who received corticosteroid injections over the same period. Another trial tracking patients for over three years found that 80.5% of those in the HA group maintained a meaningful response at 40 months, versus 65.8% in the placebo group.
Treatment protocols vary. Some HA products require a series of three to five weekly injections, while newer high-molecular-weight formulations can deliver similar results with just one or two shots. Your doctor will recommend a protocol based on the specific product used. One clinical trial found that combining corticosteroids with hyaluronic acid outperformed HA alone at every time point from one week through six months, suggesting the combination can offer both fast and sustained relief.
Platelet-Rich Plasma (PRP): Promising but Limited
PRP injections use a concentrated sample of your own blood platelets, which contain growth factors that may promote tissue healing. The idea is appealing: rather than masking symptoms, PRP could potentially help repair damaged tissue. The reality is more modest.
A large meta-analysis of 11 randomized trials covering over 1,600 patients found that PRP provided statistically better pain relief than placebo at three and six months. But by 12 months, the benefit disappeared entirely. The researchers concluded that PRP’s efficacy in knee osteoarthritis is “weak” and its clinical relevance “debatable.”
PRP is also considerably more expensive than corticosteroid or HA injections, and insurance rarely covers it. If you have mild-to-moderate osteoarthritis and haven’t responded well to other injections, PRP may be worth discussing with your doctor, but the evidence doesn’t support it as a first choice.
Stem Cell Injections: Not FDA-Approved
Stem cell injections for knee pain are heavily marketed by clinics across the country, but the FDA has been clear on this point: no stem cell products are approved for the treatment of osteoarthritis, tendonitis, or any other orthopedic condition. The only FDA-approved stem cell products are blood-forming cells derived from umbilical cord blood, and those are approved exclusively for blood disorders.
The FDA has warned that many of these products are illegally marketed, have not been shown to be safe or effective, and in some cases carry significant safety risks. Clinics offering stem cell injections for knee pain are operating outside established regulatory approval, and patients typically pay thousands of dollars out of pocket for treatments with unproven benefits.
Genicular Nerve Blocks: A Different Approach
Unlike the options above, genicular nerve blocks don’t treat the joint itself. Instead, they target the nerves that transmit pain signals from the knee to the brain. A small amount of anesthetic and corticosteroid is injected around the genicular nerves on the outside of the knee joint.
A study tracking 96 patients over nine years found that 50% of patients maintained clinically meaningful pain reduction for at least 6.9 months after a single nerve block. Most patients experienced significant pain reduction for three months or more. This option is particularly useful for people who haven’t responded well to injections inside the joint, or who have advanced arthritis and aren’t candidates for surgery yet.
If a diagnostic nerve block provides good relief, your doctor may recommend a more permanent procedure called radiofrequency ablation, which uses heat to disable the nerve and can extend pain relief for six months to a year or longer.
How to Choose Between Them
The practical decision usually comes down to where you are in your treatment journey and the severity of your osteoarthritis:
- First-time injection, acute flare-up: Corticosteroids provide the fastest relief and are widely available. They’re a reasonable starting point if you need to get pain under control quickly.
- Mild-to-moderate osteoarthritis, looking for longer relief: Hyaluronic acid injections have the strongest evidence for sustained improvement over months. They’re a better fit if you want to reduce your reliance on repeated steroid shots.
- Already tried corticosteroids and HA without success: Genicular nerve blocks offer a different mechanism that bypasses the joint entirely. PRP is another option, though the evidence is weaker.
- Considering stem cells: Wait for FDA-approved products and established clinical evidence before spending thousands on unregulated treatments.
What to Expect After an Injection
Most knee injections are done in an office visit and take just a few minutes. You can typically walk out and resume normal activities the same day, though guidelines recommend avoiding strenuous activity or heavy impact on the joint for about 48 hours. Some people experience mild soreness or swelling at the injection site for a day or two, which is normal.
Corticosteroid injections may cause a temporary “flare” where pain increases for 24 to 48 hours before the anti-inflammatory effect kicks in. Hyaluronic acid injections rarely cause flares but take longer to produce noticeable improvement. With any injection, icing the knee for 15 to 20 minutes after the procedure can help manage initial discomfort.