OBJECTIVES: To compare the efficacy and safety of collagenase clostridium histolyticum (CCH, Xiaflex®) injection with surgical fasciectomy for the treatment of Dupuytren’s contracture (DC). METHODS: Systematic review and qualitative synthesis of comparative and non-comparative studies reporting efficacy (clinical success, recurrence of contracture) and safety (complication) outcomes for patients undergoing fasciectomy for DC. Informal non-statistical comparison with outcomes from 3 pivotal placebo controlled trials and a long term follow-up study of DC patients treated with CCH. RESULTS: Sixty-eight studies of fasciectomy were identified for inclusion in the review: 61 case series (52 retrospective; 9 prospective); 3 randomised controlled trials (RCTs), none of which permitted either a direct comparison with CCH or an indirect comparison via a common comparator; 1 RCT follow-up study; 2 prospective uncontrolled studies; 1 postal survey. Studies varied in terms of fasciectomy technique employed. Follow-up ranged from only immediately post-operatively up to 35 years post-operatively. Definitions of surgical success and recurrence varied, and were frequently ill-defined or less stringent than the robust definitions used in the CCH trials. In studies of fasciectomy where definitions were judged as reasonably comparable to those used in the CCH trials (clinical success: 14 studies; recurrence: 40 studies), clinical success and recurrence rates for CCH and fasciectomy were comparable (clinical success: 63% vs 69% respectively, recurrence: 28% vs 21% at 4 years, respectively). Complication rates were greater for fasciectomy than for CCH. These included digital nerve or artery injury (3.3% vs 0%), complex regional pain syndrome (3.6% vs 0.04%), joint stiffening (8.9% vs 0%), wound infection (6.2% vs 0%), and paraesthesia (4.3% vs 0%). Tendon ruptures were reported with CCH, but were infrequent (0.07%). CONCLUSIONS: CCH and surgical fasciectomy can be reasonably considered as comparable in terms of efficacy for the treatment of DC and superior in terms of safety.