Abstract: Objective To compare the effects of roxadustat versus erythropoiesis-stimulating agents (ESAs) on anemia and cardiovascular safety in peritoneal dialysis (PD) patients.Methods A retrospective analysis was conducted on 205 PD patients who were admitted to the Second Affiliated Hospital of Xuzhou Medical University from January 2019 to January 2024. Among them, 90 patients received oral roxadustat (a roxadustat group), and 115 received ESAs (an ESA group). Both groups were compared for hemoglobin (Hb), blood lipids, blood pressure, cardiac function, and incidence of cardiovascular events before and after treatment. All patients were followed up for 48 weeks.Results Baseline Hb levels were (96.44±24.40) g/L in the roxadustat group and (95.91±16.50) g/L in the ESA group. By week 48, Hb levels significantly increased to (120.07±21.90) g/L and (117.64±19.30) g/L (P<0.001). The target achievement rate of Hb also significantly improved in both groups at week 48 (P<0.05). Cholesterol levels on week 48 significantly decreased compared to baseline in both the roxadustat (statin/non-statin) group and the ESA (statin) group (P<0.05). Baseline ejection fraction (EF) was (48.00±6.87)% in the ESA group and (49.00±6.58)% in the roxadustat group, which increased to (57.60±4.06)% and (56.00±4.97)% at week 48, respectively (P<0.05). In the high-dose ESA subgroup, mean arterial pressure significantly increased from baseline (115.0±11.3) mmHg vs. (109.0±10.2) mmHg, P<0.05, while no significant changes were observed among the roxadustat subgroups. The incidence of cardiovascular events was significantly higher in the ESA group (26 cases) than in the roxadustat group (9 cases) (P=0.017).Conclusions Roxadustat significantly improves renal anemia in PD patients, with a lower incidence of cardiovascular events than ESAs.