End-stage liver disease (ESLD) has become the main cause of mortality in patients coinfected by human immunodeficiency virus (HIV) and hepatitis B virus or hepatitis C virus in developed countries. The aim of this study was to describe the natural history of and prognostic factors for ESLD, with particular attention paid to features affecting liver transplantation. This was a prospective cohort study in 2 Spanish community-based hospitals performed between 1999 and 2004. One hundred four consecutive patients with cirrhosis and a first clinical decompensation of their chronic liver disease or hepatocellular carcinoma were included in the study. During a median follow-up of 10 months (endpoint: death, liver transplantation, or the last checkup date), 61 patients (59%) died. The probability of mortality (Kaplan-Meier method) at 1, 2, and 3 years was 43% [95% confidence interval (CI), 34%–60%], 59% (95% CI, 48%–70%), and 70% (95% Cl, 59%–81%), respectively. In a multivariate analysis, the Model for End-Stage Liver Disease (MELD) score and the inability to reach an undetectable plasma HIV-1 RNA viral load at any time during follow-up were the only variables independently associated with the risk of death (P < 0.001). Fifteen (14%) of the 104 patients were accepted for liver transplantation, although only 5 underwent the procedure, and 10 died while on the waiting list. The waiting list mortality rate in patients with a MELD score < 20 and in patients with a MELD score >20 was 58% and 100%, respectively (median follow-up, 5 months). In conclusion, HIV-1–infected patients with ESLD, especially those with poorly controlled HIV and a high MELD score, have a poor short-term outcome. The MELD score may be useful in deciding whether to indicate liver transplantation in these patients. However, because only a small proportion of the patients in this study were considered candidates for liver transplantation and most died while on the waiting list, few received a transplant. Liver Transpl 15:1133–1141, 2009. © 2009 AASLD.