Pre-exposure prophylaxis (PrEP) is a promising HIV prevention approach for men who have sex with men (MSM), however non-adherence could limit its effectiveness. Understanding the experiences of HIV-uninfected MSM taking routine medications can provide valuable insights into open label PrEP adherence in real world settings and guide development of PrEP adherence interventions. In this study, we examined self-reported medication-taking experiences and facilitators and barriers of medication adherence among a geographically-diverse online sample of HIV-uninfected US MSM. Among 1480 participants, 806 (54%) reported taking medications regularly, of whom 80% reported taking medications for treatment and 55% for prevention purposes. Facilitators of medication adherence included establishing a routine, keeping medication visible, and using a pill-box; barriers included forgetting, changes in routine, and being busy or away from home. Only 45% rated their medication-taking ability as excellent, and 36% reported not missing any doses in the past 30 days. In multivariable analyses, older men and those not reporting any adherence barriers were more likely to report excellent adherence, and men willing to use PrEP were more likely to report perfect 30-day adherence. Counseling strategies to build pill-taking routines and support younger MSM are suggested to maximize the public health impact of PrEP.