<p>The disproportionate HIV burden among young sexual minority men (YSMM) necessitates the study of neurodevelopmental decisional factors impacting transmission-relevant behaviors. We investigated the impact of behavioral regulation on condomless anal sex among YSMM, considering PrEP use, partnership type, and substance use as potential effect measure modifiers. YSMM (n = 120) completed an online baseline survey assessing behavioral regulation, PrEP use, and sociodemographics, and digital daily surveys on sexual behaviors, substance use, and partner type over eight weeks. We used modified Poisson regression, controlling for age, race, ethnicity, and education, to examine the relationship between behavioral regulation index (BRI) scores and condom use during anal sex. We used interaction terms to assess effect measure modification by substance use before or during sex and partnership type, stratified by PrEP use status. Difficulties in behavioral regulation (higher scores) increased the probability of condomless sex while using substances, but this association was not present in the absence of substance use. Behavioral regulation difficulties also contributed to a higher probability of condomless sex with main partners among PrEP non-users. Higher BRI scores were linked to condomless sex in particular contexts (i.e., sex with substances or main partners). These findings highlight the complex relationships between behavioral regulation and sexual behavior in the context of biomedical HIV prevention options and relationship dynamics for YSMM.</p>