Among doxycycline postexposure prophylaxis (doxy-PEP)-eligible men, Staphylococcus aureus tetracycline nonsusceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select for multidrug-resistant S aureus, underscoring the importance of surveillance. Among doxycycline postexposure prophylaxis (doxy-PEP)-eligible men, Staphylococcus aureus tetracycline nonsusceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select for multidrug-resistant S aureus, underscoring the importance of surveillance.