This study explored the prevalence and related risk behaviors for hepatitis C (HCV), hepatitis B (HBV), and human immunodeficiency virus (HIV) among a sample of male injection drug users (IDU) in Arak, Iran. One hundred male IDU attending methadone maintenance clinics between April and September, 2012 were enrolled and evaluated for HCV, HBV, and HIV infection. The majority of study participants (56%) had evidence of HCV exposure, 6% had evidence of HBV, and 19% were HIV-infected. Co-infections were frequent; 15% had evidence of HIV and HCV, 6% had evidence of HBV and HCV, and 5% had serologic markers for all three infections. Most (84%) were susceptible to HBV infection. A history of any syringe sharing (54%) and syringe sharing in prison (25%) were common. In bivariate analyses, a history of any syringe sharing and syringe sharing in prison were both associated with all three viral infections. The high prevalence of HCV, HBV, HIV, and co-infections among IDU in Arak is concerning and indicates rapid disease spread outside of Iran’s main urban centers. Prevention efforts should expand vaccination for IDU who are non-immune to HBV and continue to target syringe sharing with efforts such as needle exchange programs, including inside prisons.