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Objective To explore the association of serum bile acid profile with metabolic complications and outcomes in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. Methods Between December, 2013 and December, 2016, 77 patients with ESRD on maintenance hemodialysis and 30 healthy subjects were recruited from the Second Affiliated Hospital of Chongqing Medical University. Fasting blood samples were collected from all the subjects, and a targeted metabolomics approach based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the changes in serum bile acids between the ESRD patients and the healthy subjects. Univariate and multivariate analyses were performed to screen the differential bile acids between the two groups. Results Six differential bile acids were identified as probable biomarkers for differentiation between ESRD patients and healthy subjects. The levels of chenodeoxycholic acid, deoxycholic acid, and cholic acid were significantly decreased, and the levels of glycochenodeoxycholic acid, taurochenodeoxycholic acid, and glycocholic acid were significantly increased in ESRD patients(P < 0.05). Subgroup analyses suggested that the levels of taurocholic acid, taurochenodeoxycholic acid, taurohyocholic acid, and tauro α-muricholic acid all increased significantly and progressively in the order of the healthy control group, ESRD survival group, and ESRD death group(P < 0.01). Conclusion The serum bile acid profile of ESRD patients is significantly different from that of healthy subjects, suggesting the association of bile acid metabloism disorder with the occurrence of dyslipidemia and a poor prognosis of ESRD.