Throughout the world, injection drug users (IDUs) are the group at highest risk for hepatitis C virus (HCV) infection. IDUs residing in the island of Puerto Rico and Puerto Rican IDUs residing in the U.S. mainland have been shown to be at very high risk of infection with HIV. However, the extent to which HCV infection has spread among IDUs in Puerto Rico is not yet known. The aims of this study were to estimate seroprevalence of HCV and to identify the correlates associated with HCV transmission. The sample was drawn through street outreach strategies and was comprised of 400 injection drug users not in treatment, living in the San Juan metropolitan area. HCV and HIV infection were detected by enzyme-linked immunosorbent assay and the results were confirmed by Western blot. Information on sociodemographics, drug use patterns, and risk behaviors was obtained through structured interviews. Bivariate analyses and multivariate logistic regression were used to assess covariates of infection with HCV. The prevalence of HCV infection was 89%. After controlling for sociodemographic characteristics, HCV infection was positively associated with increasing years of injection, injecting in a shooting gallery, tattooing in prison, and self-reported STD infection. Notably, IDUs who had initiated drug injection within the year prior to the study interview had an HCV infection rate of 57%. This study indicates that more aggressive educational programs are urgently needed to reduce the spread of HCV infection among IDUs in Puerto Rico.