Spontaneous bacterial peritonitis (SBP) in liver transplantation (LT) recipients who progress to cirrhosis has received little attention. We investigated the adequacy of empirical treatment with third-generation cephalosporins for SBP in this population and the impact of transplantation on the evolution of the infection. We performed a cohort study with 138 SBP episodes: 19 in LT patients and 119 in non-LT patients. The etiology of SBP was identified for 73.7% of the episodes in LT patients and for 38.7% of the episodes in non-LT patients (P 5 0.004). The main microorganisms in recipients were Escherichia coli (35.7%) and Streptococcus pneumoniae (21.4%). The etiologies did not differ in non-LT patients. The cephalosporin sensitivity was similar in the 2 groups (85.7% versus 78.4%, P 5 0.7). LT recipients developed renal failure (57.9% versus 25.2%, P 5 0.004) and encephalopathy (42.1% versus 22%, P 5 0.08) more often than non-LT patients, and the mortality rates during episodes (52.6% versus 13.4%, P < 0.001) and at 6 months (70.6% versus 34.7%, P 5 0.005) were higher. According to a multivariate analysis, the mortality-associated risk factors at diagnosis were a Model for End-Stage Liver Disease (MELD) score > 18 odds ratio (OR) 5 6.1 and being an LT recipient (OR 5 4.45). At 6 months, the risk factors for mortality were a MELD score > 18 (OR 5 3.08), being an LT recipient (OR 5 3.47), a known etiology (OR 5 2.08), and the presence of hepatocellular carcinoma (OR 5 3.73). Liver Transpl 20:856-863, 2014. V C 2014 AASLD.Received January 14, 2014; accepted April 3, 2014.The treatment of choice for end-stage cirrhosis is liver transplantation (LT). Nonetheless, the recurrence of the primary disease, the development of liver cirrhosis (especially in patients with hepatitis C virus, in whom reinfection almost always occurs), and associated complications are common causes of late graft loss and have an impact on morbidity and mortality. [1][2][3][4] It is well recognized that spontaneous bacterial peritonitis (SBP) is associated with a high mortality rate (approximately 20%) in patients with cirrhosis, 5-7 and the first SBP episode predicts a significant decrease in survival, even in the short term, with 1-year survival rates ranging from 28.5% to 93%. [8][9][10][11][12][13] Nonantipseudomonal third-generation cephalosporins (3CP) are the treatment of choice for SBP, 5,6,10 but several recent studies have reported that bacterial resistance to 3CP has reached a disturbing level of 43%. 6,14 Nosocomial and health care-related infections are often associated with multidrug-resistant microorganisms such as Enterobacteriaceae producing extended-spectrum beta-