Young men who have sex with men continue to be highly affected by HIV. To improve understanding of the role that multiple co-occurring health issues (i.e., syndemics) play in HIV acquisition, sophisticated modeling methods are needed. The purpose of this study was to use structural equation modeling to understand the structure of the syndemic and to test its longitudinal association with condomless anal sex. Data are from a longitudinal study of 450 YMSM. A primary syndemic component comprised of substance use, violence, and internalizing mental health factors significantly predicted the number of condomless anal sex partners in the full sample. Analyses exploring associations by race/ethnicity found a significant association among White YMSM, but not among Black or Latino YMSM. Higher-order factor modeling suggests these psychosocial factors form a syndemic in all racial/ethnic groups, but the syndemic, as conceptualized here, may be less relevant to racial/ethnic minority YMSM.