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Female genital mutilation/cutting (FGM/C) is widely considered a human rights infringement, although communities that practice the tradition view it as an integral part of their culture. Given these vastly different views, the effectiveness of efforts to abandon FGM/C is uncertain. We conducted a systematic review of the best available evidence regarding evaluations of interventions to prevent FGM/C, including eight controlled before-and-after studies with 7,042 participants from Africa. Findings indicate that 19 of 49 outcomes (with baseline similarity) were significantly different at study level, mostly favoring the intervention, but results from four meta-analyses showed considerable heterogeneity. The limited effectiveness and weak overall quality of the evidence from the studies appear related to methodological limitations of the studies and shortcomings in the implementation of the interventions. Nevertheless, the findings point to possible advantageous developments from the interventions.