Abstract Background and Aims Peritonitis is a common and severe complication of peritoneal dialysis (PD). For comparative analysis standardized definitions are crucial, but most studies have been used heterogenous methods to measure outcomes. The ISPD 2022 guidelines have revised and clarified numerous definitions and proposed new peritonitis categories. Thus, deeper comprehension concerning the incidence, prevalence, and outcome of cause- and time specific peritonitis in contemporary cohorts is required. Method Between 1st January 2009 and 31st May 2023, 267 patients who started PD at our institution were included in the study (Tab. 1). All PD-related peritonitis episodes that occurred in our unit during the study period were collected. The new definitions and outcomes of ISPD 2022 recommendations were employed. Results During the study period 113 patients (42.3%) experienced 219 peritonitis (Tab. 2). The overall peritonitis rate was 0.25 episode/patient year. During the study period, 230 patients (88.5%) discontinued the dialytic technique; among them 122 were transferred to HD. Peritonitis represented the main cause of hemodialysis (HD) transfer (35.2%). Patient cumulative probability of remaining peritonitis-free at one year was 84.2%. The initial antibiotic regimen (cefazolin in association with tobramycin ip) was effective in 131 episodes (141/219, 64.3%), while the medical cure and refractory peritonitis rates were equal to 70.3 and 22.4%, respectively. The rates of peritonitis associated death, HD transfer, catheter removal and hospitalization were 6.8%, 18.3%, 18.7% and 64.4%, respectively. Relapsing, repeat, recurrent and enteric peritonitis accounted for 7.8%, 6.8%, 4.1% and 2.7% of all episodes, respectively. Catheter insertion, catheter related and pre-PD peritonitis were 4.2, 2.1 and 0.5%. Gram-positive and Gram-negative bacteria accounted for 74.1% and 21.3% of peritonitis, respectively. Initial antibiotic regimen was more effective in Gram-positive (76.4%) than Gram-negative (35.1%) microorganisms (p < 0.0001). Culture-negative peritonitis accounted for 25.6% of all specimens. In comparison with positive-culture peritonitis, culture-negative episodes showed a higher medical cure rate (88.4%, 46/52 vs 68.9%, 104/151; p < 0.01) and were significantly less likely to be complicated by hospitalization (48.1%, 25/52 vs 72.2%, 109/151; p < 0.05), catheter removal (9.6%, 5/52 vs 22.5%, 34/151; p < 0.05), HD transfer (9.6%, 5/52 vs 21.9%, 33/152; p < 0.05) and death (0%, 0/52 vs 8.6%, 13/151, p < 0.05). However, initial antibiotic regimen response was similar between culture-negative and culture-positive episodes (71.2%, 37/52 vs 62.3%, 94/151, p = ns). Rates of relapsing, repeat and recurrent peritonitis were 0.023, 0.018 and 0.011 episode/patient-year, respectively accounting for 7.8, 6.8 and 4.1% of all episodes The composite outcome of either catheter removal or death due to peritonitis was higher in relapsing (42.1%, 8/19, p < 0.05) and recurrent (44.4%, 4/9, p < 0.05) episodes than generic peritonitis (19.1%, 34/178) but similar to repeat peritonitis (3/15, 20%, p = ns). Although peritonitis from enteric causes represented only 2.7% of all episodes, they needed catheter removal in one-third of events (33.3%) and caused patient death (66.6%) in the remaining cases. Conclusion Although representing the leading cause of HD transfer cause, more than 50% of incident PD patients never experienced peritonitis. Carrying a worse outcome than generic peritonitis, entities such as relapsing, recurrent and enteric peritonitis should be aggressively treated. Conversely, culture-negative peritonitis showed a better prognosis as compared to positive-culture episodes. However, aiming at the prevention of microbial resistances, the reduction of culture-negative cases is necessary to minimize patient exposure to empiric therapy with multiple antibiotics. In our experience first-line empirical antibiotic therapy was effective in almost 65% of the cases. Nevertheless, the efficacy of this regimen was unsatisfactory in Gram-negative microorganisms requiring further microbiological and pharmacokinetic evaluation.