BACKGROUND Enzymatic fasciotomy with collagenase clostridium histolyticum (CCH) has revolutionized the treatment for Dupuytren’s contracture (DC). Despite its benefits, the long-term outcomes remain unclear. This study presented a comprehensive 10-year follow-up assessment of the enduring effects of CCH on patients with DC. AIM To compare the short-term (12 wk) and long-term (10 years) outcomes on CCH treatment in patients with DC. METHODS A cohort of 45 patients was treated with CCH at the metacarpophalangeal (MCP) joint and the proximal interphalangeal (PIP) joint and underwent systematic re-evaluation. The study adhered to multicenter trial protocols, and assessments were conducted at 12 wk, 7 years, and 10 years post-surgery. RESULTS Thirty-seven patients completed the 10-year follow-up. At 10 years, patients treated at the PIP joint exhibited a 100% recurrence. However, patients treated at the MCP joint only showed a 50% recurrence. Patient satisfaction varied, with a lower satisfaction reported in PIP joint cases. Recurrence exceeding 20 degrees on the total passive extension deficit was observed, indicating a challenge for sustained efficacy. Significant differences were noted between outcomes at the 7-year and 10-year intervals. CONCLUSION CCH demonstrated sustained efficacy when applied to the MCP joint. However, caution is warranted for CCH treatment at the PIP joint due to a high level of recurrence and low patient satisfaction. Re-intervention is needed within a decade of treatment.