Peritonitis is a serious complication in peritoneal dialysis (PD) patients; however, the clinical outcome of culture-negative peritonitis (CNP) is controversial. This retrospective study of CNP attempts to resolve this controversy. In 813 episodes of peritonitis, 202 episodes of CNP in 152 PD patients were reviewed. Two different methods of effluent culture were utilized during the study period. The incidence of CNP was lower with 50 ml centrifugation culture than 10 ml direct inoculation culture (20.7% vs. 35.7%; p < 0.05). The overall cure rate of CNP was greater than 80% of patients receiving cefamezine and gentamicin as initial therapy. Relapse within 30 days after completion of treatment happened in 9.6% of cases, and antibiotic therapy failed in 8.1% of CNP cases. In comparison with cured patients, patients with relapse or treatment failure are older (62.0 +/- 15.0 years vs. 54.3 +/- 15.3 years; p = 0.007) and have a higher rate of abdominal pain (91.4% vs. 69.3%; p = 0.007) and greater need for salvage therapy (54.3 % vs. 11.0%; p < 0.001). A history of antibiotic use or peritonitis within 30 days before onset of CNP was noted in 23.3% and 12.5% of cases, respectively, but was not associated with clinical outcome. The clinical outcome of CNP was benign in this study. Older age, abdominal pain, and need for salvage therapy were associated with an increased risk for relapse and treatment failure in CNP cases. Moreover, 50 ml centrifugation culture method was better than 10 ml direct inoculation culture in reducing the incidence of CNP.