Osteoarthritis is the most common and disabling of the orthopedic diseases. Currently, the conservative treatment of osteoarthritis is limited to symptomatic treatment, whose goal is to improve function and pain control. Ankle osteoarthritis is relatively uncommon, in contrast to osteoarthritis of the hip and knee, and the therapeutic options (both pharmacologic and surgical) are limited, with surgery providing poorer and less predictable results. The effectiveness of platelet-rich plasma injections for osteoarthritis is still controversial, especially so for ankle arthritis, owing to the lack of evidence in the present data. We retrospectively evaluated the mid- to long-term clinical results (mean follow-up of 17.7 months) for platelet-rich plasma injections in 20 patients (20 ankles) with ankle osteoarthritis. We evaluated the presence of pain using the visual analog scale, function using the Foot and Ankle Disability Index, and subjective satisfaction. The pre- and post-treatment scores, obtained from the clinical records and from telephone interviews during the follow-up period, were compared using the Student t test. We found a strong positive effect for 4 platelet-rich plasma injections (injected once a week) on pain (p = .0001) and function (p = .001), with 80% of patients very satisfied and satisfied, and only 2 patients (10%) required surgery because of early treatment failure. These results suggest that the use of platelet-rich plasma injection is a valid and safe alternative to postpone the need for surgery.