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Hepatitis C virus (HCV) usually evades the host’s immune system and persists as a chronic infection. Intravenous drug users (IVDU) represent the majority of patients infected with HCV Combined therapy of chronic hepatitis C (CHC) with peginterferon a-2a and ribavirin can be successful even when patients continue the intravenous drug use. In this study, we compared the characteristics of age, gender, genotype, and stage of fibrosis and the therapy outcome among IVDU and patients with no history of drug use. The study included 69 patients diagnosed with chronic hepatitis C, evaluated and treated at the Clinic for infectious diseases in Nis from 2005 to 2009. HCV RNA was detected by a polymerase chain reaction and the determination of genotypes was undertaken. Liver biopsies were examined histopathologicaly. Patients received a combined treatment of peginterferon alfa-2a and ribavirin. Therapy efficiency was evaluated based on the achievement of the sustained virological response (SVR). A comparison of characteristics was performed with the use of Mann-Whitney U test, chi-square (χ2) test and logistic regression. IVDU were significantly younger than patients in the control group. Prevalence of stage 1 fibrosis was significantly higher among IVDU. The therapy outcome is influenced by the patient’s age and HCV genotypes. Each year added to one patient decreased the therapy efficiency by 8.1%, while genotypes 2 and 3 experienced a therapy which was 2.08 times more efficient than in other cases. IVDU represent a specific population different from non-using patients. However, they can be treated effectively if an adequate patient-doctor relationship is established.