tBackground: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostlyderived from treatment of selected patients enrolled in clinical trials. This study aimed to assess theeffectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy.Methods: Independent observational multicentre study including consecutive patients receiving Peg-interferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the startof the study.Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retro-spective and 2073 in the prospective phase.Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase:325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) duringthe prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%).During multivariate analysis genotypes 2/3 were significantly associated with higher sustained viro-logical response rates; cirrhosis and �-glutamil-transpeptidase >2 times the normal limit were associatedwith poorer response.Conclusions: The response to Peg-interferon/ribavirin therapy in “real world” clinical practice is distinctlylower than in registration trials. The difference in response rates was more pronounced among easy-to-treat than among difficult-to-treat hepatitis C virus genotypes.© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved