Hepatitis C virus (HCV) has infected an estimated 170 million people worldwide, most of whom are chronically infected (60% to 80%). In Italy, the estimate of anti-HCV antibody (Ab) prevalence, in the general population of Northern Italy, is 3.2%; in Central and Southern Italy, it is 8.4% to 22.4%. Highest prevalence of infection (70% to 90%) is found among intravenous drug users. Our purpose is to monitor HCV infection among drug users treated in a Drug Addiction Centre (Ser.T) in Naples and to gain a better understanding of that relationship with the abused substance(s). Epidemiological data are shown for viral coinfections. Finally, the authors investigate access to specific HCV therapy in an Italian Ser.T. The study analyzed a group of 1753 consecutive subjects treated from 1988 to 2008 in the O.U. Ser.T D.S.31 (Gesù e Maria Hospital), ASL Napoli 1 Centre. HCV Abs were detected by enzyme immune assay method and confirmed by recombinant immunoblot assay III method. During the entire period, we performed real-time polymerase chain reaction at random for 312 patients. The incidence (per year) of HCV infection showed a rapid spread decrease from 49.5% in 2003 to 14.5% in 2008. The overall prevalence of HCV was 48.1%. We tested 312 randomly selected patients for viral replication. Our study showed active viral replication in 201 (64.4%) patients as follows: 97 of 201 (31.1%) resulted infected by genotype (gt) 1; 3 of 201 (1.0%) gt 2; 84 of 201 (26.9%) gt 3; and 4 of 201 (1.3%) gt 4. Coinfection data showed that HCV Ab prevalence was 58.5% (48 of 82) in hepatitis B virus chronically infected patients. Human immunodeficiency virus (HIV)/HCV coinfection resulted in 95.2% (80 of 84) HIV patients. The prevalence of HIV Abs in HCV-infected patients was 8.99% (80 of 889). Analysis of drug abuse showed high prevalence of opiate addicted, multiabusers, and with high-risk factors. Cocaine abuser prevalence was 14.4%, and incidence, during past 4 years of the study, rose to 42.6%. Alcohol abuser prevalence represented 5.8% of patients and incidence rose to 17.7% in final 4 years of the study. In those opiate addicted, HCV infection was 61.0% (805 of 1320). HCV infection in cocaine-addicted patients was 9.5% (24 of 253). In 78 delta-9-tetra-hydro-cannabinol addicted patients, 5.1% of tests were positive (4 of 78). In alcohol abusers, HCV infection was 9.8% (10 of 102). Access to HCV treatment in our cohort from 2000 to 2008 resulted low (15.4%). Enhancing the Ser.Ts efficiency can result in health and financial benefits.