Background. There have been few reports on the causes and treatment outcomes for nosocomial spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis. Methods. We performed a retrospective cohort study to compare the microbiological and clinical characteristics in nosocomial versus community-acquired SBP. All patients with SBP, for whom culture was proven to be positive for SBP at Samsung Medical Center (Seoul, Republic of Korea) from 1 January 2000 through 31 June 2007, were included. Medical records and laboratory data were reviewed. Nosocomial SBP was defined as SBP diagnosed after 72 h of hospitalization. Results. A total of 236 patients with SBP were enrolled (mean age ±SD age, 56.6±10.7 years); 166 patients were women, and 70 were men. Nosocomial and community-acquired SBP occurred in 126 and 110 patients, respectively. Escherichia coli accounted for 102 (43.2%) of 236 isolates, Klebsiella species accounted for 33 isolates (14.0%), and Streptococcus species accounted for 23 isolates (9.8%). The overall 30-day mortality rate for nosocomial SBP was higher than that for community-acquired SBP (58.7% vs. 37.3%; P=.001). Nosocomial isolates of gram-negative organisms were significantly more resistant to third-generation cephalosporins (41% vs. 10.0%; P<.001) and quinolones (50.0% vs. 30.9%; P=.003), compared with community-acquired isolates. Multivariate analysis revealed that nosocomial infection, concomitant hepatocellular carcinoma, presentation with acute renal failure or shock, and resistance to third-generation cephalosporins were significant risk factors for 30-day mortality associated with SBP. Conclusions. Nosocomial SBP has a poorer outcome than community-acquired SBP. The resistance to third-generation cephalosporins for gram-negative organisms, which are more common in nosocomial cases of SBP than in community-acquired cases of SBP, adversely affects the outcome of SBP in patients with liver cirrhosis.