The aim of this study was to evaluate the clinical characteristics and outcome of spontaneous bacterial peritonitis, a serious complication in patients with cirrhosis and ascites, in an HIV-infected cirrhotic population. Thirty-five HIV-infected cirrhotic patients who developed spontaneous bacterial peritonitis during a 12-year period were compared with 70 non-HIV-infected cirrhotic subjects. Patients were matched according to the date of the first episode of spontaneous bacterial peritonitis. A bacteriological diagnosis was made in 37 of 47 (79%) and in 50 of 97 (52%) episodes in the HIV group and in the non-HIV group, respectively (p=0.003), and Streptococcus pneumoniae was isolated more frequently in the HIV group (22 vs. 8%, p=0.02). Median survival after the initial diagnosis of spontaneous bacterial peritonitis was 2.9 and 14.0 months in the HIV group and non-HIV group, respectively. Age (hazard ratio [HR] 1.04; 95%CI 1.01-1.07), male sex (HR 2.55; 95%CI 1.34-4.83), Child-Pugh score at first spontaneous bacterial peritonitis episode (HR 1.29; 95%CI 1.10-1.54), renal impairment at first spontaneous bacterial peritonitis episode (HR 2.61; 95%CI 1.49-4.62), and HIV infection (HR 9.81; 95%CI 4.03-23.84) were independently associated with higher long-term mortality after the first diagnosis of spontaneous bacterial peritonitis. In conclusion, HIV-infected cirrhotic patients with spontaneous bacterial peritonitis have a higher rate of bacteriological diagnosis and a more frequent pneumococcal etiology than non-HIV-infected subjects. Life expectancy in these patients, once spontaneous bacterial peritonitis has developed, is poor. These data are particularly relevant for determining the optimal time for liver transplantation in this population.