Elevated total serum alkaline phosphatase levels have been associated with higher mortality in the general population, chronic kidney disease patients, and hemodialysis patients. However, in peritoneal dialysis patients, this association has received little attention. The aim of this study was to evaluate the association between alkaline phosphatase and all-cause mortality in peritoneal dialysis patients. In this single center retrospective cohort study, 1,366 incident peritoneal dialysis patients from January 1, 2000 to December 31, 2021 with baseline serum alkaline phosphatase values were enrolled. Collected baseline data included demographic characteristics and clinical and laboratory measurements. All patients were followed until December 31, 2021. The associations of total serum alkaline phosphatase levels with all-cause mortality were assessed using multivariable-adjusted Cox models. Mean age of patients was 61.0 (± 14.2) years, 55.8% of patients were men, 24.5% of patients were diabetic, and 6.8% had previous history of cardiovascular disease. The median serum alkaline phosphatase level was 76.0 U/L (interquartile range=60.0–96.0 U/L). During a 6,746.9 person-years of follow-up period, 429 patients died. After adjusting for demographics, comorbid conditions, and laboratory parameters, the highest alkaline phosphatase tertile group was significantly associated with a hazard ratio for all-cause mortality of 1.47 (95% confidence interval, 1.12 to 1.93, P=0.006). Each standard deviation higher baseline alkaline phosphatase level was associated with 34% (95% confidence interval, 1.25 to 1.44, P<0.001) higher risk of all-cause mortality. Higher total serum alkaline phosphatase levels in patients with peritoneal dialysis were independently associated with all-cause mortality.