Background The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear.The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years.Methods This study was a retrospective,controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cirrhosis.Of these,86 patients received lamivudine 100 mg daily accompanied with general intal treatment,and the other 67 were given general intal treatment only.Significant clinical responses were recorded after years of antiviral treatment.Results The patients in both groups were matched in terms of age,sex and laboratory results at baseline.After years of therapy,the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group.The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group.Genotypic resistance tyrosine,methionine,aspartate,aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment,and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine.Conclusions Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression,and significantly improves hepatic function and prognosis.However,the use of a retrospective control cohort precludes drawing definitive conclusions.