Men who have sex with men (MSM) in Bangkok may experience multiple psychosocial health conditions, such as substance use, suicidality, and a history of sexual abuse. These factors may contribute to HIV vulnerability in a syndemic way. A syndemic is defined as a number of synergistically interacting health conditions producing excess disease in a population. The objective of this study is to examine whether psychosocial health conditions among MSM have a syndemic association with HIV prevalence and HIV incidence. To do this, we evaluated psychosocial health conditions and their associations with unprotected sex, HIV prevalence and HIV incidence in a cohort of Thai MSM (N = 1,292). There was a positive and significant association between the number of psychosocial health conditions and increased levels of unprotected sex and HIV prevalence at study baseline. The number of psychosocial health conditions at baseline was also associated with increased HIV incidence during follow-up (no conditions, HIV incidence = 15.3 %; one to three conditions, 23.7 %; four to five conditions, 33.2 %). The number of psychosocial health conditions was positively associated with HIV risk behavior and HIV prevalence and incidence. Prevention efforts among MSM need to address the existence of multiple psychosocial health conditions and their synergy to effectively decrease the spread of HIV infection.