Background <p>Bile acids (BAs) are now recognized as endocrine hormones involved in glucose and lipid metabolism regulation and inflammation control. Recent studies have also shown the association of BAs level in chronic kidney disease progression and hemodialysis patients’ prognosis. However, their role in peritoneal dialysis (PD) is unknown. Therefore, based on a longitudinal cohort, this study aims to explore the relationship of BAs and all-cause mortality in PD patients.</p> Methods <p>A retrospective cohort study was conducted involving 517 PD patients. Serum BAs level prior to PD catheterization were collected. Restricted cubic spline (RCS) analysis with full adjustment was used to characterize the dose-response relationship between serum BAs and all-cause mortality. Cox proportional hazards regression models were performed to assess the independent association between BAs levels and all-cause mortality.</p> Results <p>A total of 517 patients were included. During a median follow-up of 3.65 (1.36, 5.46) years, death occurred in 210 of 517 (40.6%) patients. The relationship between BAs levels and the risk of all-cause mortality was fitted using multivariate RCS adjusted for clinical relevant factors showing that BAs levels were linearly associated with all-cause mortality (p for non-linearity = 0.589). Further Kaplan-Meier survival analysis revealed a significantly higher all-cause mortality risk in the high BAs group (log rank score 13.04, <i>p</i> &lt; 0.001). Cox regression showed that elevated BAs levels were an independent risk factor for all-cause mortality in PD patients (HR = 1.056, 95% CI: 1.005–1.109, <i>p</i> = 0.031) after adjusting for confounding factors.</p> Conclusion <p>Elevated pre-dialysis serum BAs levels are independently associated with increased all-cause mortality in PD patients. Serum BAs may represent a potential prognostic indicator, although further validation is required before clinical application.</p>