BACKGROUND: Several methods of debridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established. METHODS: This systematic review and meta-analysis was conducted to find the best available evidence for the effect of debridement on diabetic foot wound outcomes. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011 for randomized controlled studies (RCTs) and observational comparative studies. RESULTS: We identified 11 RCTs and three nonrandomized studies reporting on 800 patients. The risk of bias was moderate overall. Meta-analysis of three RCTs showed that autolytic debridement significantly increased the healing rate (relative risk [RR], 1.89; 95% confidence interval [CI] 1.35-2.64). Meta-analysis of four studies (one RCT) showed that larval debridement reduced amputation (RR, 0.43; 95% CI, 0.21-0.88) but did not increase complete healing (RR, 1.27; 95% CI, 0.84-1.91). Surgical debridement was associated with shorter healing time compared with conventional wound care (one RCT). Insufficient evidence was found for comparisons between autolytic and larval debridement (one RCT), between ultrasound-guided and surgical debridement, and between hydrosurgical and surgical debridement. CONCLUSIONS: The available literature supports the efficacy of several debridement methods, including surgical, autolytic, and larval debridement. Comparative effectiveness evidence between these methods and supportive evidence for other methods is of low quality due to methodologic limitations and imprecision. Hence, the choice of debridement method at the present time should be based on the available expertise, patient preferences, the clinical context and cost.