Treatment of hepatitis C is based on the combination of peginterferon alfa-2a or -2b plus ribavirin; the more effective peginterferon for this purpose has not been established. The aim of this study is to compare the effectiveness of hepatitis C treatment according to the type of peginterferon used. A prospective cohort study was performed from November 2002 to May 2004, with up to 12 months of follow-up in all patients after completion of treatment. The study included naïve monoinfected patients, divided into two groups: Group A: peginterferon alfa-2a plus ribavirin and Group B: peginterferon alfa-2b plus ribavirin. The main variables studied were plasma glutamate pyruvate transferase levels (biochemical response), viral load (virologic response), and treatment effectiveness (biochemical and virologic response). A total of 202 patients were studied (Group A: 87; Group B: 115), there were no significant differences in baseline characteristics between the two groups. Sustained biochemical response: 75.8% vs. 76.2% (P = .908); Sustained virological response: 71.3% vs. 64.3% (P = .293); Effectiveness of treatment: 64.2% vs. 60.87% (P = .628). No differences in the sustained virological or biochemical response were found between groups receiving peginterferon alfa-2a or peginterferon alfa-2b plus ribavirin, suggesting that the two types of peginterferon alfa are similarly effective for treating hepatitis C in monoinfected patients.