Introduction. In Europe, injectable collagenase clostridium histolyticum (CCH) is a novel, minimally invasive, non-surgical therapy with efficacy in correcting Dupuytren's contracture (DC). We evaluated the efficacy and tolerability of 5 CCH injections using a protocol designed to follow clinical practice. Methods. This was a 20-center, 9-month, open-label study in which DC patients with primary flexion deformities 20° (100° for MP; 80° for PIP) received 3 CCH (0.58 mg) injections/joint (5 injections/patient) at 30-day intervals. The primary endpoint was clinical success, defined as a reduction in contracture to 5° 30 days after the last injection (“Day 30”). After first injection into a prioritized joint, patients opted to receive up to 2 more injections into the same cord or cords from other affected joints whether or not they achieved clinical success with the first joint. Adverse events (AEs) were monitored. Results. For the primary endpoint, 71% of MP (n=343) and 41% of PIP (n=244) joints showed a reduction in contracture to 5° with CCH injections. Of joints that did not achieve clinical success, 66% of MP (n=100) and 38% of PIP joints (n=144) showed 50% reduction in contracture after CCH. For range of motion (ROM), mean±SD increase from baseline to Day 30 was 33.0±16.2° for MP and 27.5±18.5° for PIP joints. Most commonly reported AEs were localized edema, bruising, pain, swelling, and tenderness; most resolved without intervention. Two serious AEs, deep vein thrombosis in the leg and tendonitis with partial tendon/ligament injury, were deemed possibly and probably related to treatment, respectively. Conclusions. Results from this open-label study, designed to follow clinical practice, provide support for the efficacy of CCH in correcting the flexion deformity of MP/PIP joints caused by DC. Clinical success and ROM improvements were comparable to those observed in randomized, placebo-controlled trials. This study was funded by Auxilium Pharmaceuticals, Inc