The aim of the project was to study human immunodeficiency virus (HIV) incidence, sociodemographic and behavioral correlates of HIV acquisition among injection drug users (IDUs). A total of 717 IDUs were recruited, tested, and counseled for HIV-1; 466 HIV-negative participants were enrolled and followed-up at 6 and 12 months. Sociodemographic and behavioral data were collected during each study visit. The association of sociodemographic and behavioral factors to HIV-1 incidence was assessed. During the 9-month recruitment period, 717 IDUs were screened and 466 participants were enrolled. HIV-1 prevalence at baseline was 35%. Most enrolled subjects were young (median age 30), male (75%), injected heroin in the previous 3 months (86%), about 50% had shared syringes and other paraphernalia, and 44% had unprotected sex in the last month. The retention rate at the 12-month follow-up was 72% and the adjusted retention rate was 88%. The HIV incidence rate was 7.2/100 person-years. HIV incidence was significantly associated with specific drug risk behaviors, including injecting the mixture of heroin and psychostimulants, the frequency of injecting in groups with other people, and having more drug dealers. The St Petersburg IDUs cohort demonstrates one of the highest HIV incidence rates in the world. In 2004 to 2006, the HIV incidence was 4.5, in 2005 to 2007-19.6, and in 2008 to 2009-7.2/100 person-years. The peak of HIV epidemic among IDUs in St Petersburg, as determined by 3 independent cohort studies, was in 2006 to 2007. Interventions targeting IDUs with long experience of heroin injection and high levels of injection risk behaviors are urgently needed.