The appropriate use of pre-exposure prophylaxis (PrEP) by men who have sex with men (MSM) can be highly effective at reducing HIV transmission. Our review examined prevalence estimates, sexual behaviors, and medication adherence among MSM PrEP users in high-income countries. Articles published between January 2008 and December 2018 were identified through Medline, Web of Science, CINAHL, and CENTRAL. The search identified 643 publications, of which 52 were included in the final synthesis. We found that PrEP initiation was not consistently associated with significant changes in sexual behavior, but some users may have risk compensated. A minority of MSM used PrEP, and they had high levels of adherence. PrEP-related stigma, side effects, and psychosocial factors lead to nonadherence. A daily routine, pill boxes, alarms/texts, and education can promote adherence. Further research is required to examine PrEP impact on sexual behavior and factors that influence adherence in high-risk MSM subpopulations.