Background. Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure.Methods. We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation.Results. We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI],. 54-.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI,. 43-.82).Conclusions. Initiation of ART significantly reduced the rate of hepatic decompensation by 28%-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease. © 2013 The Author.