<p>Young men who have sex with men (YMSM) have high HIV incidence but suboptimal PrEP coverage, so it’s critical we identify barriers to PrEP uptake and persistence. Among people living with HIV, research indicates that medication adherence is lower among people who believe that alcohol and HIV medications interact to produce toxic effects. Rates of hazardous drinking are elevated among YMSM, suggesting such beliefs may be common. The goal of these analyses was to examine how alcohol-interactive toxicity beliefs impacts PrEP uptake and discontinuation in a sample of 478 HIV-negative YMSM. This sample had a mean age of 23.0 (SD = 2.8) and was racially and ethnically diverse (24.1% Black; 29.9% White; 36.2% Hispanic/Latino). Longitudinal models examined the direct effects of alcohol consumption and toxicity beliefs, as well as their interaction, on PrEP uptake and discontinuation six months later. Most YMSM endorsed at least one toxicity belief (58%). Among baseline non-PrEP-users, toxicity beliefs were associated with lower PrEP uptake (aHR = 0.76; 95% CI: 0.61–0.95). Among current PrEP users, YMSM with both higher alcohol consumption and toxicity beliefs were those most likely to discontinue PrEP six months later. This study provides new evidence that the prevalence of alcohol-related interactive toxicity beliefs among YMSM are substantial and represent a barrier to effective HIV prevention. Given PrEP efficacy depends on consistent use, discontinuation during periods of HIV risk undermines prevention goals. Interventions addressing alcohol-related toxicity beliefs—through education, counseling, and tailored messaging—may optimize PrEP uptake and persistence, particularly among populations with high alcohol use.</p>