Flaviviridae–hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV) – and human immunodeficiency virus (HIV) frequently show similar modes of transmission. HCV and GBV-C/HGV infection was assessed in 134 consecutive patients with evidence of HIV infection, living in Campania, Italy. Data obtained from this cohort were compared with those obtained from 252 age- and sex-matched HCV infected patients without evidence of HIV infection (HCV control group). Following enzymatic immunoassays, samples were tested for the presence of HCV-RNA by RT-PCR. The HCV-RNA positive sera were genotyped by LiPA procedure. The prevalence of HCV infection in HIV patients was 19.40% and the largest group of HIV–HCV co-infected patients (84.62%) was represented by intravenous drug users (IVDU). The distribution of HCV genotypes in HIV–HCV patients was different, compared to that observed in HCV control group. HCV genotypes 1a (50%) and 3a (23.08%) were more frequently detected in HIV–HCV patients, compared to HCV control group (5.16 and 5.56% for 1a and 3a, respectively). Conversely, HCV genotypes 1b (55.70%) and 2a/2c (30.26%) were more represented in HCV control group, compared to HIV–HCV patients (15.38 and 0% for 1b and 2a/2c, respectively). GBV-C/HGV seroprevalence was 41.04% in HIV patients and 6.54% in healthy control individuals. Differently from HCV, GBV-C/HGV infection did not correlate to a preferential risk behaviour in the HIV cohort. Comparative analysis of HCV and GBV-C/HGV infection indicates that the use of injecting drugs might play a key role in the epidemiology of HCV and, in particular, of 1a and 3a HCV genotypes, in HIV patients.