Introduction. Chronic wounds are characterized by impaired tissue physiology that stalls healing. The prevalence of wound chronicity presents challenges in wound management and health care cost-containment. Objective. This comparative effectiveness study evaluates the value proposition of 2 collagen-containing wound dressings — oxidized regenerated cellulose (ORC)/collagen/silver-ORC dressing and ovine collagen extracellular matrix (ECM) — in matched cohorts of patients undergoing treatment for diabetic foot ulcers (DFUs). Materials and Methods. Data extracted from the US Wound Registry identified DFUs treated with either dressing and included wounds with complete data records (n = 3230). Thirty-seven variables were considered in propensity score matching to develop a case-matched cohort of 844 DFUs (n = 422 DFUs/group). Results. The ORC/collagen/silver-ORC dressing group yielded a significantly higher percentage of DFUs that healed or improved (82% vs. 74.6%; P = .0096). The ovine collagen ECM dressing group yielded a significantly higher percentage of DFUs that worsened (15.2% vs. 23.9%; P = .0013). The ORC/collagen/silver-ORC dressing group demonstrated a higher percentage of DFUs that attained 75% to 100% granulation at zero depth at 4, 8, 12, and 16 weeks. Median time to 75% to 100% granulation was 42 days for the ORC/collagen/silver-ORC dressing group versus 60 days for the ovine collagen ECM dressing group (P = .0109). Conclusions. According to this comparative effectiveness study using real world data, ORC/collagen/silver-ORC dressing appears to afford improved healing and reduced time to granulation relative to ovine collagen ECM dressing.