Background: Reducing the risk of transfusion transmitted infections (TTI) is one of the main concerns of blood transfusion systems. Evaluation of HCV risk factors in HCV infected blood donors is critical for donor selection and ensuring blood safety. The aim of this study was to evaluate known and putative risk factors of HCV infection in Iranian blood donors. Methods: This matched case-control study was conducted on serologically confirmed HCV positive blood donors (cases) and serologically negative HCV blood donors came back to Iranian Blood Transfusion centers over the country from November 2015 to May 2017. Cases and controls were matched by donation status and interviewed for demographic, medical, and risk histories. Penalized conditional logistic regression model with backward selection method was used in data analysis. STATA software version 13 was used for statistical analysis.