The HIV epidemic in Latin America is highly concentrated in men who have sex with men (MSM). In the United States, multiple co-occurring psychosocial conditions have been shown to act as intertwined epidemics to potentiate HIV transmission among MSM. To date, no study has examined the role of syndemics and condomless sex among MSM in Latin America. In 2012, an online survey was conducted among members of the largest social/sexual networking website for MSM in Latin America. Participants were asked about demographics, sexual behaviors, HIV/STI diagnoses, and psychosocial well-being, including depression, suicidal ideation, hazardous alcohol use, hard drug use during sex, history of childhood/adolescent sexual abuse, intimate partner violence, and sexual compulsivity. Multivariable logistic generalized estimation equations were used to assess the relationship of syndemic factors and (1) engagement in higher risk condomless anal sex and (2) self-report of prior HIV diagnosis. Among 24,274 survey respondents, 74.6 % of the sample had at least one syndemic factor. In an additive model, syndemics were associated with increased odds of higher risk condomless anal sex, ranging from adjusted odds ratio of 1.31 (95 % CI 1.20, 1.43) for one syndemic factor to 4.06 (95 % CI 3.25, 5.09) for 6/7 syndemic factors. Similarly, syndemics were associated with increased odds of HIV infection (p < .0001). This study provides initial evidence that intertwined syndemics increase HIV risk behavior and HIV infection among MSM in Latin America. In the Latin American context, comprehensive HIV prevention interventions for MSM should be developed and tested that simultaneously address co-occurring psychosocial conditions and HIV risk.