Abstract Introduction The purpose of this study was to review and compare clinical outcomes between percutaneous needle fasciotomy (PNF) and collagenase Clostridium histolyticum (CCH) injection for the treatment of Dupuytren’s contracture. Materials and Methods A systematic review was performed including all level I-III evidence studies investigating the clinical outcomes of PNF and CCH injection in the treatment of Dupuytren’s contracture. Results Five studies (278 CCH patients, 225 PNF patients; 285 CCH fingers, 246 PNF fingers, 405 males, and 98 females) were analyzed. Two randomized studies were level I evidence, one randomized study was level II, and two nonrandomized studies were level III. Two studies analyzed a total of 205 patients, each demonstrating statistically superior outcomes in one outcome measure (contracture improvement and Michigan Hand Questionnaire (MHQ) satisfaction subscore) with PNF, while the remaining three studies demonstrated no significant differences in outcomes between the two techniques. Three studies reported a statistically higher rate of minor complications (local pain, edema, ecchymosis, lymphadenopathy, pruritis) with CCH, while the remaining two studies demonstrated no significant difference in complication rates. Conclusion For the treatment of Dupuytren’s contracture, there is some evidence that suggests superior clinical outcomes of PNF compared with CCH and a higher minor complication rate with CCH.