OBJECTIVES: Assess the clinical effect of clostridial collagenase ointment (CCO) relative to undifferentiated wound dressings in the outpatient care setting for the treatment of venous leg ulcers (VLU). METHODS: Retrospective de-identified electronic medical records from 2007-2013 were extracted from the Intellicure Limited Data Set (I-LDS). The I-LDS extracts records from 96 hospital-based outpatient wound centers. A propensity score model using a 3 to 1 nearest neighbor matching approach was performed to test for treatment effect and adjust for covariance between wounds that received CCO and wounds treated with undifferentiated wound dressings.  RESULTS: A total of 9,314 patients, 22,312 wounds, and 186,023 visits for VLU were identified. The majority of patients was female (51.9%) with an average age of 61.6 (SD=17.7). Approximately 21.3% had a history of hypertension, 8.3% had a history of venous insufficiency with diabetes, and 2.5% received immunosuppressive agents. The mean wound surface area was 7.9cm (SD=14.4). The average wound age was 8.5 months (SD=27.8) and the average treatment duration was 2.9 months (SD=4.9). Of the 22,312 wounds, approximately 13.2% received CCO (n=2,954). The average number of CCO tubes used by patients was 2.6 (SD = 1.2). The average total visits where CCO was administered was 5.6 (SD = 16.2) and the average days of use with CCO was 12.3 (SD = 41.3). VLUs treated with CCO were significantly more likely (p<0.005) to improve over the course of therapy relative to wounds treated with undifferentiated wound dressings alone.  CONCLUSIONS: This analysis indicates that CCO provides a clinical benefit in the management of VLUs. Over the course of therapy VLUs treated with CCO demonstrate greater clinical improvement than VLUs treated with undifferentiated wound dressings.