Introduction: Insulin resistance is a common finding in chronic hepatitis C and there are some data confirming a relationship between impaired insulin sensitivity and poor response to treatment with pegylated interferon and ribavirin. The aim of the study was to determine the efficacy of combination antiviral therapy with pegylated interferon and ribavirin in relation to insulin resistance measured by homeostasis model assessment-insulin resistance (HOMA-IR) in chronic hepatitis C (CHC). Materials and methods: The study group comprised 82 patients with biopsy-proven CHC who received standard treatment with pegylated interferon in a dose of 1.5 ug/kg body-weight/week and a weight-based daily dose of ribavirin. Overnight fasting glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (y-GT), and insulin level were examined in all patients before treatment. Insulin resistance was calculated using HOMA-IR. The biochemical parameters and HOMA index of sustained viral responders and non-responders were compared. Results: Forty-six patients (56.1%) achieved sustained viral response (SVR) and treatment failure was noted in 36 (43.9%). Patients who achieved SVR were younger (mean age 40.9±13 vs. 50.2±1.2 years; p=0.0009, had less advanced liver disease (mean fibrosis score 1.4±0.9 vs. 2.2±1.2; p=0.003), and differed with respect to y-GT level (51.8±39.4 vs. 81±72.8; p=0.02). HOMA-IR did not differ between the groups (4.6±5.0 vs. 5.55±5.35; p=0.45) nor did BMI (25.4±4.4 vs. 26.5±4.2; p=0.3). Conclusions: Insulin resistance is a common finding in chronic hepatitis C, but it must be used with caution as a prognostic factor of SVR to antiviral treatment. Younger patient age, lower degree of fibrosis, and lower y-GT activity remain the best predictors of response to pegylated interferon and ribavirin.