In November 2008, the Norwegian Knowledge Centre for Violence and Traumatic Stress Studies (NKVTS) commissioned the Norwegian Knowledge Centre for the Health Services (NOKC) to do a systematic review about the effectiveness of interventions to prevent female genital mutilation/cutting (FGM/C). The review would answer the question: What is the effectiveness of interventions designed to reduce the prevalence of female genital mutilation/cutting compared to no or any other intervention? We searched systematically for relevant literature in international scientific databases, in databases of international organisations that are engaged in projects concerning FGM/C, and in reference lists of relevant reviews and included studies. We selected studies according to pre-specified criteria and appraised the methodological quality using checklists. We summarized the results using tables and calculated effect estimates (adjusted absolute risk difference and risk ratio) in outcomes for which pre- and post scores for both intervention and comparison groups were reported. We included and summarized results from six controlled before-and-after studies. All studies were set in Africa and compared an intervention with no intervention (except one study which included an educational module). There was great variation in prevalence, ethnicity, religion, and education among these settings. All studies were judged to have weak methodological quality and the quality of the evidence was low. The effect estimates suggest that 1) training health personnel likely produced no effects in knowledge or beliefs/attitudes about FGM/C; 2) educating female students may possibly have led to a small increase in knowledge/awareness about FGM/C; 3) multifaceted community activities may possibly have increased the proportion of participants having favourable cognitions and intentions about FGM/C; 4) community empowerment through education may possibly have positively affected prevalence of FGM/C, participants' knowledge about the consequences of FGM/C, and regrets about having had daughter cut. However, the low quality of the body of evidence affects the interpretation of results and raises doubts about the validity of the findings. There is a paucity of high quality evidence regarding the effectiveness of interventions to prevent FGM/C and the evidence base is insufficient to draw solid conclusions. While first-generation anti-FGM/C intervention studies are informative, there is an urgent need for additional studies. Such second-generation studies should be randomized or at a minimum secure similar distribution of prognostic factors in the intervention and comparison groups; long-term to ensure viability and reliable assessment of changes in prevalence; take into account regional, ethnic and sociodemographic variation in the practice of FGM/C; focus on prevalence – assessed by physical examinations – behaviours, and intentions; and they should be cross-disciplinary, if possible through international collaborative initiatives.