The impact of highly active antiretroviral therapy (HAART) on progression to end-stage liver disease (ESLD) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection remains controversial. We studied 157 HCV+ haemophilic men (85 HIV+ and 72 HIV-), on whom dates of HIV and HCV seroconversion and clinical outcomes were known. Time to ESLD was determined by Kaplan-Meier product-limit methods and risk factors for ESLD progression were analysed by a Cox proportional hazards model. Among HIV+ men, ESLD was more common, 17 of 85 (20.0%) than in HIV-, eight of 72 (11.1%) and median ESLD-free survival significantly shorter, P = 0.009, hazard ratio 3.00 [95% confidence interval (CI): 1.27-7.08]. HAART treated HIV+ had longer ESLD-free survival than HIV+ untreated, 30.3 vs. 20.0 years, P = 0.043, hazard ratio, 3.14 (95% CI: 1.27-7.08), comparable with survival in HIV- men, P = 0.13, hazard ratio 2.20 (95% CI: 0.76-2.35). Progression was unrelated to HAART toxicity (n = 0) or HCV antiviral therapy (n = 7). HIV+ HAART Rx and HIV- did not differ in HCV duration, age at ESLD, age at death or present, overall or AIDS mortality, all P > 0.05. These data suggest that HAART improves ESLD-free survival, approaching that in HIV- men.