Abstract: Objective  To systematically evaluate the efficacy and safety of long-acting and short-acting erythropoiesis-stimulating agents (ESAs) for the treatment of renal anemia in patients with maintenance hemodialysis (MHD).  Methods  We searched the Cochrane Library, Web of Science, Embase, PubMed, China Journal Full-Text Database, VIP Information Chinese Journal Service Platform, and WanFang Data Knowledge Service Platform to obtain literature on ESAs. The search period was up to June 30, 2025. RevMan 5.4 software was used to screen and analyze the randomized controlled trials.  Results  A total of 16 studies involving 3,961 patients were included in the meta-analysis. Meta-analysis showed that no significant differences were found between long-acting and short-acting ESAs in terms of hemoglobin increase range [MD=-0.05, 95% CI：(-0.19, -0.09), P=0.480], hemoglobin response rate [RR=0.97, 95% CI：(0.92, 1.02), P=0.280], ferritin level [MD=7.90, 95% CI：(-14.81, 30.61), P=0.500], and transferrin saturation level [MD=0.16, 95% CI：  (-1.08, 1.40), P=0.800] in MHD patients. Subgroup analysis based on treatment interval of long-acting ESAs indicated that patients receiving Darbepoetin alfa once every 1～2 weeks had a greater increase in hemoglobin level than those receiving short-acting ESAs [MD=0.13, 95% CI：(0.11, 0.15), P＜0.001]. In contrast, patients receiving Methoxy Polyethylene Glycol-Epoetin beta once a month had a lower increase in hemoglobin level than those receiving short-acting ESAs [MD=- 0.29, 95% CI：(-0.42, -0.16), P＜0.001]. The risk of cardiovascular and cerebrovascular thromboembolism was lower in patients receiving long-acting ESAs than those receiving short-acting ESAs [RR=0.85, 95% CI：(0.75,0.97), P=0.020]. There were no statistically significant differences between the two groups in terms of respiratory tract infection [RR=1.13, 95% CI：(0.89,1.43),P=0.330], gastrointestinal diseases [RR=0.98, 95% CI：(0.89,1.07), P=0.600], hypertension [RR=1.06, 95% CI：(0.91, 1.23),P=0.470], mortality [RR=0.98, 95% CI：(0.78,1.24), P=0.880], and the incidence of total adverse events [RR=0.96, 95% CI：(0.91,1.02), P=0.220].  Conclusion  There are no significant differences in improving hemoglobin indicators between long-acting and short-acting ESAs for MHD patients. However, long-acting ESAs are better in increase of hemoglobin level with a lower risk of cardiovascular and cerebrovascular thromboembolism.

Key words: Hemodialysis, Long-acting ESA, Short-acting ESA, Efficacy, Safety