The objective of this case series was to determine the efficacy and safety of combined treatment with ribavirin and peginterferon alpha-2a in sickle cell disease (SCD) patients with chronic hepatitis C virus (HCV) hepatitis. Eight patients in King Abdulaziz Hospital & Oncology Center, Jeddah, Kingdom of Saudi Arabia from 2003 and 2006 with chronic HCV infection were treated with peginterferon alpha-2a and ribavirin for one year. All 8 patients had a complete early virological response. Seven out of 8 had an end of treatment response with undetectable HCV RNA at the end of therapy, 5 of whom also maintained a sustained virological response when assessed 6 months after the end of treatment. Hemoglobin concentrations measured at one, 3, 6, 9, and 12 months of treatment showed no significant changes from that measured as baseline. Treatment of chronic HCV hepatitis in patients with SCD with peginterferon alpha-2a and ribavirin seems safe and effective.