While classical opportunistic infections have decreased as the main cause of hospital admission of HIV-infected patients, other conditions including drug-related toxicities seem to have increased. We assessed the proportion of patients with hospital admission due to antiretroviral (ARV)-related toxicities over the last 7 years at a single HIV/AIDS reference institution located in Madrid. A total of 1981 consecutive hospital admissions in 1581 different HIV-infected patients were analyzed. Nearly half of them (45%) were on ARV therapy. Overall, ARV-related toxicities were the main or secondary reason for hospital admission in 141 patients (7%). Liver toxicity was the most frequent complication (n = 42; 30%), of which one-third were associated with NVP use and 80% occurred in subjects with underlying chronic hepatitis C virus (HCV) infection. Other main ARV-related toxicities were bone marrow toxicity due to zidovudine (17%), pancreatitis (13%), and indinavirassociated nephrolithiasis (6%). Eight patients presented with symptomatic hyperlactatemia, two of them with lactic acidosis. All subjects with ARV-related toxicities had a favorable outcome, except one with prior HCVrelated end-stage liver disease, who died after experiencing hepatic decompensation following initiation of a protease inhibitor-based regimen.