ABSTRACTBackground: Hepatitis C virus (HCV) infection is global health problem with an estimated 415,000 deaths in 2015. The objective of this study was to explore the direct and indirect effects of risk behaviors on HCV infection among male PWIDs (people who inject drugs) in Kermanshah, Iran.Methods: We surveyed 606 male PWIDs in Kermanshah city. Data on demographic characteristics and risk behaviors associated with HCV infection were gathered through structured interviews. The participants were recruited from two drop-in centers using snowball sampling. We used path analysis to explore the direct and indirect effects of risk behaviors on HCV infection among male PWIDs.Results: Over half of the 606 participants had been exposed to HCV with 54.80% having a positive test for HCV antibodies. Older Age of first of drug injection [B Coefficient: –0.03, 95% confidence interval (CI): −0.04, −0.01] and regular attendance at harm-reduction programs (B Coefficient: −0.21, 95% CI: −0.43, −.01) reduce the chance of HCV exposure. Longer duration of injection (B Coefficient: 0.09, 95% CI: 0.06, 0.12) was associated with higher probability of HCV exposure.Conclusion: This study implies that age of first of drug injection, regular attendance at harm-reduction programs and duration of injection had both direct and indirect effects on HCV infection.