Enzymatic debridement with collagenase is a technique that is commonly used in clinical practice. This systematic review examines the effect of collagenase on all kinds of wounds, compared to an alternative therapy, on wound healing, wound bed characteristics, cost-effectiveness and the occurrence of adverse events. We conducted a systematic literature search on available literature in Cochrane databases, MEDLINE, EMBASE and CINAHL. Two investigators independently assessed the titles and abstracts of all randomised controlled trials obtained involving collagenase of all kinds of wounds based on inclusion criteria. Of the 1411 citations retrieved, 22 studies reported outcomes with the use of collagenase either for wound healing or wound debridement. Results support the use of collagenase for enzymatic debridement in pressure ulcers, diabetic foot ulcers and in conjunction with topical antibiotics for burns. However, studies presented a high risk of bias. Risk ratio of developing an adverse event related to collagenase versus the alternative treatment was statistically significant (for 10 studies, RR: 1·79, 95% CI 1·24-2·59, I =0%, P = 0·002). There is very limited data on the effect of collagenase as an enzymatic debridement technique on wounds. More independant research and adequate reporting of adverse events are warranted.