Introduction. Clostridial collagenase ointment (CCO) is the only enzymatic agent indicated for debriding chronic dermal ulcers that is approved by the United States Food and Drug Administration. Objective. The objective of this study is to estimate health care spending among patients with Stage 3 and Stage 4 pressure injuries (PIs) and patients with diabetic foot ulcers (DFUs) who experienced early (ie, within 30 days of index diagnosis) versus late (31 to 90 days of index diagnosis) initiation of CCO. Methods. Patients with PIs and DFUs between January 2007 and March 2017 were identified. One-to-one matched cohorts were used to compare all-cause health care spending and disease-related health care spending between the early initiation and late initiation groups. Results. Compared to the early CCO initiation group, all-cause health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. Compared to the early CCO initiation group, disease-related health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. All computations were statistically significant. Conclusions. Early initiation of CCO provides both all-cause and disease-related health care savings to payers and persons managing patients with PIs or DFUs. Payers, providers, and facilities should consider mechanisms to encourage the early use of CCO to lower costs.