ObjectiveThis study aimed to evaluate and compare the efficacy and safety of methoxy polyethylene glycol-epoetin beta, a continuous erythropoietin receptor activator (CERA), and roxadustat in the management of renal anemia among patients undergoing maintenance hemodialysis (MHD).MethodsA retrospective analysis was conducted involving 60 patients with renal anemia receiving MHD at a single center between December 2024 and June 2025. Participants were assigned to one of two treatment groups (n = 30 per group). The CERA group received intravenous methoxy polyethylene glycol-epoetin beta at a starting dose of 100 μg, administered every 2–6 weeks with dose adjustments based on hemoglobin (Hb) levels. The roxadustat group received oral roxadustat capsules, initiated at 100 mg three times weekly, with dose modifications ranging from 20 to 150 mg according to Hb responses. After 6 months of treatment, the primary outcome was the between-group difference in Hb change from baseline to month 6. Secondary outcomes included Hb target attainment, defined strictly as 110–130 g/L, and hypertension rate. Missing baseline covariates were imputed using k-nearest neighbors (k = 10) before overlap weighting. The overlap-weighting model included baseline Hb, age, sex, primary kidney disease, hypertension at baseline, baseline parathyroid hormone, body weight, baseline C-reactive protein, dialysis vintage, prior ESA type/dose, baseline ferritin, and baseline transferrin. The weighted Hb outcome model was a mixed model for repeated measures including treatment group, time, treatment-by-time interaction, and baseline Hb. Weighted generalized estimating equation models were used for binary repeated outcomes.ResultsAfter overlap weighting, baseline Hb was 93.0 (14.49) g/L in the roxadustat group and 93.0 (15.79) g/L in the CERA group. At month 6, weighted mean Hb was 103.4 (14.87) g/L and 111.7 (10.23) g/L, respectively. The 6-month difference in least-squares mean Hb change for CERA versus roxadustat was 8.27 (1.87, 14.67) (P = 0.012). Weighted Hb target attainment at month 6 was 37.9% in the roxadustat group and 50.6% in the CERA group; the month 6 treatment-by-time interaction RR was 1.16 (0.26–5.11) (P = 0.846). Weighted hypertension rates at month 6 were 60.7% and 57.5%, respectively; the month 6 treatment-by-time interaction RR was 0.95 (0.57–1.57) (P = 0.834).ConclusionIn this small retrospective cohort, CERA was associated with a larger 6-month Hb increase than roxadustat after overlap weighting. Hb target attainment and hypertension-rate comparisons did not show statistically significant treatment-by-time interaction effects. Because treatment allocation reflected clinical practice and patient preference, residual selection bias remains an important competing explanation.