Objectives <p>This study aims to explore the varying association of different bilirubin levels on the prognosis of peritoneal dialysis patients, with particular emphasis on the relationship between the initial occurrence of peritonitis and bilirubin levels, which has not been well elucidated in existing literature.</p> Materials and methods <p>This single-center retrospective study enrolled end-stage renal disease patients who underwent peritoneal dialysis catheter placement at Tongji Hospital from January 1, 2009, to December 31, 2023. Follow-up was conducted until October 31, 2024. To explore the relationship between the development of peritonitis and bilirubin levels, we utilized Cox proportional hazards regression models, Spearman correlation analysis, and restricted cubic spline plots.</p> Results <p>This study included 426 patients, with the sum of 106 episodes of peritonitis were documented, of which 57 were first-time occurrences, making for an incidence rate of 0.09 episodes per patient-year. Patients with total bilirubin (TBil) levels below 3.69 µmol/L (<i>P</i> = 0.008, HR = 1.919, 95% CI: 1.188–3.099) or direct bilirubin (DBil) levels below 1.46 µmol/L (<i>P</i> &lt; 0.001, HR = 2.969, 95% CI: 1.755–5.023) exhibited a greater likelihood of peritonitis occurrence compared to those in the higher-level groups.</p> Conclusion <p>Serum bilirubin, especially total and direct bilirubin, exhibits association with the risk of initial peritonitis occurrence in patients undergoing peritoneal dialysis (PD). Low levels of total and direct bilirubin are associated with an increased risk of the initial onset of peritonitis in patients undergoing peritoneal dialysis.</p> Clinical trial number <p>Not applicable.</p>