No studies have evaluated the efficacy of hyaluronic acid (HA) in reducing pain caused by osteochondritis dissecans (OCD) of the ankle. We report our initial results with this treatment. Fifteen subjects aged 18 to 60 treated for OCD of the talus were followed for 26 weeks, in a pre- and post-treatment repeated measurements design, after receiving three weekly injections of intra-articular HA. The efficacy of HA injections in reducing pain and improving function was assessed at each visit and adverse events were recorded. Efficacy was evaluated by comparing scores determined using a Visual Analog Scale for pain, stiffness and function over time with baseline values. In addition, frequency of symptoms and global function over time were assessed using questionnaires and the AOFAS Ankle-Hindfoot Scale. Data analysis was made using ANCOVA models and paired t-tests. All statistical tests were based on an alpha level of 0.05. The majority of subjects were male (60%) and had Grade 3 lesions (60%). Mean VAS scores, reported on a scale from 1 (e.g., no pain) to 10 (e.g., worst pain) decreased for pain (5.6 to 3.2), stiffness (5.1 to 2.9), and function (5.9 to 3.3) from baseline to week 26. Subjective global function scores, reported on a scale from 0 to 100 (with 100 representing healthy, pre-injury function), improved on average from 57.3 at baseline to 74.3 by week 26. All of these results were statistically significant, as was the decrease in frequency of pain reported by subjects at the end of the study. OCD of the ankle treated with intra-articular injections of HA caused a decrease in pain scores and increase in global functioning over a short period of time (within 12 weeks) which then lasted for more than 6 months with minimal adverse events.