Peritonitis remains a common complication of peritoneal dialysis (PD). The aim of this study was to analyze, in a PD center, long-term temporal trends in peritonitis rates, microbiology and outcomes. We treated 588 cases of peritonitis that occurred during 11,833.6 months at risk. Y-set and twin-bag disconnecting systems were introduced in 1990, mupirocin at the exit site in 2000 and fluconazole prophylaxis in 2005. Vancomycin and ceftazidime were the empiric protocol. Global and 5-year cohort rates were expressed as episodes/patient-year (ep/p-y). A global peritonitis rate reduction was found from 1.02 to 0.47 ep/p-y (p = 0.008). Poisson analyses performed in each of the subgroups of Gram-positive and Gram-negative peritonitis revealed no significant changes over time. No case of vancomycin resistance was identified. There was a downward trend in peritonitis-related hospitalization over time to 0.11 ep/p-y (p ≤ 0.001). Trend analysis showed a favorable, but changing evolution, highlighting the importance of accurate longitudinal PD center registry data and quality control.