Background/Aims-Although the antiviral and histological benefits of peginterferon/ribavirin therapy are well established, the effects on health-related quality of life (HRQOL) and sexual health † This is publication number 14 from the HALT-C Trial Group. ‡ Financial support: Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: H.L. Bonkovsky is a consultant, is on the speakers' bureau, and receives research support; P.F. Malet receives research support; R.K. Sterling is a consultant, on the speakers' bureau, and receives research support; R.J. Fontana is a consultant and on the speakers' bureau; A.M. Di Bisceglie is a consultant, on the speakers' bureau, and receives research support; and T.R. Morgan is on the speaker's bureau and receives research support. Other financial relationships related to this project are: H.L. Bonkovsky receives research support from Bayer Diagnostics; P. Methods-Subjects completed SF-36 and sexual health questionnaires prior to and after 24 weeks of peginterferon/ribavirin therapy (n = 1144). Three hundred and seventy-three (33%) subjects were HCV RNA negative at week 20 and continued therapy through week 48; 258 were seen at week 72. One hundred and eighty achieved sustained virological responses (SVR) and 78 relapsed.Results-At baseline, patients had poorer scores for all eight SF-36 domains compared to healthy controls. Patients with cirrhosis had lower HRQOL scores than those with bridging fibrosis, as did patients with higher depression scores. SVR patients had significant improvements in seven domains, whereas relapsers had significant worsening in one domain. Sexual scores improved in SVR patients and decreased in relapsers (p = 0.03). In multivariate analyses, improvements in HRQOL and sexual scores were significantly associated with SVR but were less striking in patients with lower depression scores.Conclusions-Achievement of SVR after peginterferon/ribavirin therapy improves HRQOL and sexual health in chronic hepatitis C patients with advanced fibrosis or cirrhosis.