Background: Peritoneal dialysis is a type of dialysis performed by patients in their homes; patients receive training from dialysis clinic staff. Peritonitis is a serious complication of peritoneal dialysis, most commonly caused by gram-positive organisms. During March‒April 2019, a dialysis provider organization transitioned ~400 patients to a different manufacturer of peritoneal dialysis equipment and supplies (from product A to B). Shortly thereafter, patients experienced an increase in peritonitis episodes, caused predominantly by gram-negative organisms. In May 2019, we initiated an investigation to determine the source. Methods: We conducted case finding, reviewed medical records, observed peritoneal dialysis procedures and trainings, and performed patient home visits and interviews. A 1:1 matched case–control study was performed in 1 state. A case had ≥2 of the following: (1) positive peritoneal fluid culture, (2) high peritoneal fluid white cell count with ≥50% polymorphonuclear cells, or (3) cloudy peritoneal fluid and/or abdominal pain. Controls were matched to cases by week of clinic visit. Conditional logistic regression was used to estimate univariate matched odds ratios (mOR) and 95% confidence intervals (CIs). We conducted microbiological testing of peritoneal dialysis fluid bags to rule out product contamination. Results: During March‒September 2019, we identified 157 cases of peritonitis across 15 clinics in 2 states (attack rate≍39%). Staphylococcus spp (14%), Serratia spp (12%) and Klebsiella spp (6.3%) were the most common pathogens. Steps to perform peritoneal dialysis using product B differed from product A in several key areas; however, no common errors in practice were identified to explain the outbreak. Patient training on transitioning products was not standardized. Outcomes of the 73 cases in the case–control study included hospitalization (77%), peritoneal dialysis failure (40%), and death (7%). The median duration of training prior to product transition was 1 day for cases and controls (P = .86). Transitioning to product B (mOR, 18.00; 95% CI, 2.40‒134.83), using product B (mOR, 18.26; 95% CI, 3.86‒∞), drain-line reuse (mOR, 4.67; 95% CI, 1.34‒16.24) and performing daytime exchanges (mOR, 3.63; 95% CI, 1.71‒8.45) were associated with peritonitis. After several interventions, including transition of patients back to product A (Fig. 1), overall cases declined. Sterility testing of samples from 23 unopened product B peritoneal dialysis solution bags showed no contamination. Conclusions: Multiple factors may have contributed to this large outbreak, including a rapid transition in peritoneal dialysis products and potentially inadequate patient training. Efforts are needed to identify and incorporate best training practices, and product advances are desired to improve the safety of patient transitions between different types of peritoneal dialysis equipment.