Few studies have been conducted in the Eastern Mediterranean region on chronic hepatitis C virus (HCV) infection with reference to genotypes. We investigated the response to standard combination therapy (pegylated interferon/ribavirin) of different genotypes of HCV in Kuwaiti patients and factors that could be associated with sustained virological response (SVR). The records of all Kuwaiti patients treated for chronic HCV between January 2003 and May 2009 were retrospectively identified and reviewed. Of 108 patients studied, 27.8% were infected with genotype 1, 25.0% with genotype 3 and 47.2% with genotype 4. Overall, 64.8% of patients achieved SVR, 25.9%, were non-responders and 9.3% were relapsers. Baseline viral load and alanine aminotransferase level in addition to early virological response to pegylated interferon-based therapy may serve as a decision tool for clinicians to identify patients who are unlikely to achieve SVR.