Understanding bridging behaviors of clients of female sex workers (FSWs) is important for projecting and intervening in the spread of sexually transmitted infections in Vietnam. The goals of the study were to determine HIV/STI prevalence amongst different bridging groups, identify factors associated with being potential and active bridgers, and assess the association of drug use and unsafe sex with HIV and/or STI prevalence. In April, 2007, 292 clients were anonymously interviewed at sex venues in a two-stage time-location cluster sampling survey, followed by HIV, syphilis, and HSV-2 testing. Based on condom use with both high-risk (FSWs) and low-risk (wives/girlfriends) sexual partners, clients were classified as unlikely, potential, or active bridgers. The majority of clients were potential or active bridgers (55.8%) who had a significantly higher prevalence of herpes simplex type 2 (HSV-2) (21% and 33%, respectively) than unlikely bridgers (8.7%). HIV seropositivity was 4.4-fold (95% CI 1.1-17.1) higher among those who were HSV-2-positive. Clients of FSWs may be playing a major bridging role in transmitting HIV and sexually transmitted infections (STIs) in Vietnam. An observed synergistic interaction between drug use and condom slippage/breakage emphasizes the importance of proper condom use, particularly among drug users.