Abstract We retrospectively evaluated 232 continuous ambulatory peritoneal dialysis (CAPD) patients entering our program from January 1, 1987, to December 31, 1997, for polymicrobial peritonitis. Polymicrobial peritonitis occurred in 16% of the patients (polymicrobial-peritonitis group), whereas 52% of the patients had peritonitis episodes with only a single organism (single-organism group), and 32% of the patients had no episode of peritonitis. Polymicrobial peritonitis accounted for 8% of the 554 peritonitis episodes, occurred after 23 ± 20 months on peritoneal dialysis (PD), and was preceded by greater than three episodes of peritonitis in 73% of the patients. Peritonitis rates were greater in the polymicrobial-peritonitis group compared with patients in the single-organism group (1.8 versus 1.2 episodes/patient-year; P < 0.001). The majority of polymicrobial infections involved gram-negative and/or fungal pathogens, but in 21% of the episodes, only gram-positive organisms were identified. An intra-abdominal process was identified in only 7% of the patients. Catheter loss overall was greatest in the polymicrobial-peritonitis group (65% versus single-organism group, 30% versus patients without peritonitis, 5%; P < 0.001), but only 33% of the polymicrobial infections resulted in catheter loss. At last follow-up, 70% of the patients in the polymicrobial-peritonitis group had permanently transferred to hemodialysis compared with 25% from the single-organism group and 15% from the no-peritonitis group (P < 0.001). In conclusion, polymicrobial peritonitis is an infrequent but serious complication of CAPD that occurs late in the course of PD and is often preceded by recurrent episodes of peritonitis. Polymicrobial peritonitis is rarely the result of a catastrophic intra-abdominal process, and although the majority of patients can be successfully treated without catheter removal, the long-term prognosis is poor, with a high rate of transfer to hemodialysis.