A total of 2768 MSM participated in a survey in southern Vietnam. Univariate and multivariate logistic regression analyses were performed to determine predictors of HIV infection. The prevalence of HIV among MSM was 2.6 %. HIV infection was more likely in MSM who were older, had a religion, had engaged in anal sex with a foreigner in the past 12 months, previously or currently used recreational drugs, perceived themselves as likely or very likely to be infected with HIV, and/or were syphilis seropositive. MSM who had ever married, were exclusively or frequently receptive, sometimes consumed alcohol before sex, and/or frequently used condoms during anal sex in the past 3 months were less likely to be infected with HIV. Recreational drug use is strongly associated with HIV infection among MSM in southern Vietnam. HIV interventions among MSM should incorporate health promotion, condom promotion, harm reduction, sexually transmitted infection treatment, and address risk behaviors.