OBJECTIVES:  Oral pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine has been shown to be effective in reducing the risk of HIV infection in men who have sex with men (MSM). The aim of our study was to systematically review the existing evidence on the cost-effectiveness of PrEP in MSM. METHODS:  We performed a systematic PubMed literature search to identify relevant studies published from January 2000 through February 2016 in English or German. A study was included if it reported cost per quality-adjusted life year (QALY) estimates for the USA, Canada, Australia, or European countries. All monetary values were converted to euros. RESULTS:  Eight studies on the cost-effectiveness of PrEP in MSM, which reported results for the USA, Canada, and Australia, were included in the review. Most studies focused on the evaluation of PrEP use in the general MSM population and/or in high-risk MSM. Two studies additionally assessed the cost-effectiveness of PrEP use in monogamous serodiscordant relationships. Results varied considerably across and within studies, with some scenarios yielding incremental cost-effectiveness ratios (ICERs) of several hundred thousand euros per QALY. In studies that assessed PrEP use in high-risk MSM as well as in the general MSM population, strategies targeting high-risk MSM resulted in lower ICERs than strategies without differentiation by risk status. Three studies even showed that targeting high-risk MSM could lead to cost savings. CONCLUSIONS:  Since results of the included studies varied considerably, it is difficult to draw a clear conclusion on the cost-effectiveness of PrEP in MSM. However, in studies that evaluated PrEP use in both high-risk MSM and the general MSM population, strategies targeting high-risk MSM were found to be more cost-effective. None of the currently available studies reported results for European countries. Hence, future models evaluating the cost-effectiveness of PrEP in MSM should address this research gap.