Objectives: Hepatitis C virus (HCV) is one of the major public health problems worldwide which is transmitted through contact with infected blood or blood products. One of the most prevalent modes of HCV transmission is injecting drug with unclean needles or syringes. Therefore intravenous drug users (IVDUs) are the most important group who should be considered. The aim of this study was to evaluate seroprevalence and risk factors of hepatitis C virus in IVDUs population. Methods: The cross-sectional study was carried out on intravenous drug users who attended health and social care Drop-in centers during November 2008 to February 2009 in Isfahan province, Iran. Data was gathered using interviewer-administered questionnaire including demographic characteristics and main risk factors for HCV infection. 5ml venous blood sample was obtained from each subject. The HCV-Ab test was performed on all blood samples by ELISA. The data was analyzed using descriptive statistical methods and multiple logistic regressions by SPSS software, version 15. Results: The mean age of participants was 31.77 ± 8.51. 503 (94.7%) were men and 28 (5.3%) were women. HCV seroprevalence was 47.1% (95% CI: 42.9, 51.3). The multiple logistic regressions demonstrated that history of tattooing (OR 1.72, 95% CI 1.02-2.90), history of imprisonment (OR 2.49, 95% CI 1.40-4.42) and sharing needles/syringes (OR 2.76, 95% CI 1.54-4.95) are significant predictors of risk of HCV in IVDU population. Conclusions: In conclusion, according to the high prevalence of HCV infection among IVDUs and high adds of HCV infection from tattooing, sharing of needles/syringes and imprisonment, effective harm reduction programs should be expanded among IVDUs to prevent new HCV infections.