50 patients with Dupuytren’s contracture were randomized to treatment with either collagenase clostridium histolyticum injection or percutaneous needle fasciotomy. Patients were assessed for rates of clinical improvement, clinical success, recurrence, and adverse events at 30 days, 1-year, and 2 years after treatment. Both groups demonstrated an early 30-day clinical improvement, however, the rate of clinical improvements and success in both groups declined at 1 and 2 years. There were no significant differences between groups in clinical improvement or success over the 2-year follow-up. The recurrence rate at 2 years was 83% in the collagenase group and 68% in the fasciotomy group. Collagenase injections were associated with significantly higher rates of edema and local pain after treatment in comparison to needle fasciotomy.