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Collagenase clostridium histolyticum (CCH) injection is an alternative to surgery for patients with Dupuytren disease (DD) of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. The success of surgical and nonsurgical treatment modalities for DD is reported to vary widely between 25% and 80% (J Bone Joint Surg Am. 1985;67:1439–1443; Plast Reconstr Surg. 2007;120:44e–54e; J Bone Joint Surg Am. 2007;89:189–198; J Hand Surg Am. 2011:36:936–942; J Hand Surg Am. 1990;15:755–761; J Hand Surg Br. 1996;21:797–800; J Bone Joint Surg Br. 2000;82:90–94; Plast Reconstr Surg. 2005;115:802–810; Ann Plast Surg. 2006;57:13–17). This study presents the outcomes of patients with DD contractures treated with CCH injections at a single institution.An institutional review board–approved retrospective study was conducted of patients with DD of the hand treated with CCH injections in a single institution from February 2010 to April 2015. All patients received the recommended dose of 0.58 mg of CCH and returned for joint manipulation the following day. Data for follow-up at 7 and 30 days postoperatively and up to 5 years for patients who returned seeking further therapy for recurrent symptoms were reviewed.One hundred thirteen patients with a total of 146 affected joints (72 MCP; 74 PIP) were treated with CCH injections (95 males; 18 females; age, 40–92 y). Successful CCH therapy occurred in 75% of injected joints (109/146 joints; 59 MCP; 50 PIP), as defined by less than 5 degrees of contracture after treatment. Twenty-three percent of treated joints had partial correction (34/146 joints; 13 MCP; 21 PIP), as defined by between 5 and 30 degrees of residual contracture after treatment. Three patients (2%) had a failure of treatment, as defined by unchanged or worsened contracture from pretreatment baseline measurements. Fifteen patients (13%) returned to the clinic seeking additional therapy for recurrent joint contracture symptoms in 17 joints over a span of 1.5 months to 4 years after initial successful or partially successful treatment (17/143, 12%; 5 MCP; 12 PIP). Recurrence was defined as patients who sought treatment for a return of symptoms or greater than 20 degrees contracture in the setting of a palpable cord after initial full or partial contracture correction.Our 5-year outcome of CCH injections for DD contractures revealed full correction in 75% and partial correction in 23% of treated joints, with failure of treatment seen in only 2% of patients. Thirteen percent of the patients returned for additional treatment because of symptoms resulting from contracture recurrence in 12% of initially corrected or partially corrected joints. These positive outcomes are comparable with current surgical treatment modalities (J Hand Surg Am. 1990;15:755–761; J Bone Joint Surg Am. 1962;44B:602–613; J Clin Epidemiol. 2000;53:291–296). The use of CCH injections is an important nonsurgical treatment alternative for DD contractures of the MCP and PIP joints.