Among men who have sex with men (MSM), acute alcohol consumption is associated with higher rates of condomless anal intercourse, which is linked with a greater likelihood of exposure to HIV and other sexually transmitted infections. While pre-exposure prophylaxis (PrEP) to prevent HIV infection has become more widespread in this population in recent years, so too have concerns that PrEP uptake may be associated with health risk behaviors. This study investigated differences in sexual behaviors and drug use habits between PrEP users and nonusers in a sample of moderate- and heavy-drinking MSM. Results indicated that PrEP use was associated with riskier sexual practices, weaker self-regulatory cognitions related to condom use, and more frequent illicit drug use. These findings suggest that moderate-and heavy-drinking MSM who use PrEP may comprise a unique risk group that could benefit from targeted counseling or other interventions to reduce their risk of negative health consequences.