<p>The Thai government addresses human immunodeficiency virus (HIV) incidence by providing free Pre-Exposure Prophylaxis (PrEP) to reduce infection rates and expand access among at-risk populations. This qualitative study used the Capability, Opportunity, Motivation, and Behavior (COM-B) model to explore barriers and facilitators to PrEP adherence among Thai men who have sex with men (MSM) in Bangkok. In-depth, semi-structured interviews were conducted with 12 Thai MSM. Data were thematically analyzed and then mapped to the COM-B framework. Seven key barriers were identified: difficulty keeping medication on hand; limited awareness; cost concerns; stigma related to HIV and sexual behavior; fear of long-term side effects; substance use; and low perceived HIV risk. Twelve facilitators emerged, including: reminder tools, follow-up calls, and ease of access; self-efficacy; peer and community support; inclusive and flexible services; media and public campaigns; trust in PrEP and healthcare providers; aversion to condoms; routine integration of PrEP; distrust of partners; perceived threat and susceptibility; and self-care motivations. All participants had access to government-provided free PrEP, which supported adherence. The findings, organized through the COM-B framework, identified key determinants of PrEP adherence among Thai MSM. This application of COM-B demonstrates its utility as an analytical lens for structuring behavioral determinants in adherence research. Future research should develop targeted interventions addressing these specific COM-B components to enhance PrEP adherence in this population and extend to more diverse groups, thereby strengthening Thailand’s HIV prevention strategies.</p>