Peritonitis is a well-known cause of mortality in peritoneal dialysis (PD) patients. We carried out a retrospective study to disclose the clinical spectrum and risk profile of peritonitis-related mortality. We analyzed 693 episodes of infectious peritonitis suffered by 565 patients (follow-up 1149 patient-years). Death was the final outcome in 41 cases (5.9% of episodes), peritonitis being directly implicated in 15.2% of the global mortality and 68.5% of the infectious mortality observed. In 41.5% of patients with peritonitis-related mortality, the immediate cause of death was a cardiovascular event. Highest mortality rates corresponded to fungal (27.5%), enteric (19.3%), and Staphylococcus aureus (15.2%) peritonitis. Multivariate analysis disclosed thatthe baseline risk of peritonitis-related mortality was significantly higher in female [relative risk (RR) 2.13, 95% confidence interval (CI) 1.24-4.09, p = 0.02], older (RR 1.10/year, CI 1.06-1.14, p < 0.0005), and malnourished patients (RR 2.51, CI 1.21-5.23, p = 0.01) with high serum C-reactive protein (s-CRP) levels (RR 4.04, CI 1.45-11.32, p = 0.008) and a low glomerular filtration rate (RR 0.75 per mL/minute, CI 0.64 -0.87, p < 0.0005). Analysis of risk after a single episode of peritonitis and/or subanalysis restricted to peritonitis caused by more aggressive micro-organisms disclosed that overall comorbidity [odds ratio (OR) 1.21, CI 1.05-1.71, p = 0.005], depression (OR 2.35, CI 1.14-4.84, p = 0.02), and time on PD at the time of the event (OR 1.02/month, CI 1.00-1.03, p = 0.02) were other predictors of mortality. In summary, the etiologic agent is a definite marker of peritonitis-related mortality but gender, age, residual renal function, inflammation (s-CRP), malnutrition, and depression are other significant correlates of this outcome. Most of these risk factors are common to cardiovascular and peritonitis-related mortality, which may explain the high incidence of cardiovascular event as the immediate cause of death in patients with peritonitis-related mortality.