Vietnam is in the midst of an expanding HIV epidemic, primarily driven by an increase in injection drug use in young people. This study was conducted to understand the patterns and initiation of drug use, and the sexual risk behavior among youth in three provinces in southern Vietnam. A cross-sectional survey was conducted among male and female drug users under age 25 recruited from drug treatment centers (N = 560) and the community (N = 240) in Ho Chi Minh City, Dong Nai and Ba Ria-Vung Tau. The majority of those surveyed (82%) began by smoking heroin; after a year, 57% were injecting heroin and/or opium. Initiation of drug use frequently occurred in entertainment venues. Among injectors, 23% shared needles; 71% of all users were sexually active of whom 77% had unprotected sex. More than half of those recruited from treatment centers had previously been in drug treatment. Public health programs to prevent and treat the dual epidemics of HIV and drug abuse must be able to access and respond to the needs of youth, many of whom are unemployed and exposed to drug traffic.