The Kidney Disease Outcomes Quality Initiative guidelines for peritoneal dialysis (PD) emphasize the need for quality improvement interventions to improve outcomes in PD. Here, we report 17 years experience of initiatives focused on lowering peritonitis rates in a single PD program. This institutional review board-approved retrospective analysis used a PD registry containing prospectively collected data on patient demographics, initial Charlson comorbidity index (CCI), peritonitis, and clinical outcomes, including reasons for transfer to hemodialysis. Periods were analyzed based on quality initiatives: 1990 - 1991, baseline; 1992 - 1995, randomized controlled trial of exit-site infection prophylaxis comparing mupirocin cream applied daily to the exit site with oral cyclical (every 12 weeks) rifampin; 1996 - 1999, compact assist device introduced for spiking on the cycler; 2000 - 2004, randomized controlled trial comparing daily gentamicin cream with mupirocin as exit-site prophylaxis; and 2005 - 2007, gentamicin prophylaxis implemented as routine care (2005) and retraining of all patients (2006). Infection rates and technique failure rates in each period were compared with baseline rates using incident rate ratio analysis. A total of 382 PD patients were evaluated [median age: 50 years (range: 18 - 90 years); 54% women; 19% African American; 36% with diabetes; median CCI: 5 (range: 2 - 14)]. The peritonitis rate declined from 0.5 episodes per year at risk in 1990 - 1991 to 0.25 episodes per year at risk in 2005 - 2007 (p < 0.004). The exit-site infection rate declined from 0.72 episodes per year at risk to 0.1 episodes per year at risk over the same period (p < 0.0001). The percentage of patients transferring to hemodialysis did not change significantly over time (overall 14%, varying from 12% to 17% annually), nor did the mortality rate, which varied from 115 per 1000 years to 171 per 1000 years. We conclude that quality improvement initiatives can reduce infection rates in PD patients.