Objective To investigate the efficacy and adverse effects of different non-calcium-phosphate binders on the treatment of hyperphosphatemia in patients with end-stage kidney disease undergoing peritoneal dialysis. Methods A total of 124 patients with hyperphosphatemia undergoing peritoneal dialysis who were initially treated with non-calcium-phosphate binders agent were enrolled in the Department of Nephrology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from May in 2019 to March in 2021. Among them, 61 cases were treated with sevelamer and 63 cases were treated with lanthanum carbonate. Serum phosphorus, serum calcium, parathyroid hormone(PTH), 25-OH-VitD, alkaline phosphatase level and abdominal aortic calcification score (AACS) before and after treatment were compared in sevelamer or lanthanum carbonate treated groups, furthermore, the pill burden and cost were evaluated. Results The median follow-up time was 16.9 (9.0, 27.2) months until the end of October 2021. Serum phosphorus level was (1.70±0.31), (1.52±0.24) and (1.60±0.34) mmol/L at 1st, 3rd and 6th month after treatment, respectively, and significantly decreased than baseline [(2.08±0.31) mmol/L, P<0.05]. After 1 month and 3 months of treatment, the compliance rate in the lanthanum carbonate treated group was higher than that in the sevelamer treated group (27.0% vs 8.2%, P=0.006; 63.5% vs 39.3%, P=0.007); while after 6 months of treatment, there was no significant difference in PTH level and 25-OH-VitD level between sevelam treated group and lanthanum carbonate treated group[324.3 (178.1, 469.7) ng/L vs 304.4 (165.8, 413.3) ng/L, P=0.414; 15.01 (11.98, 22.75) nmol/L vs 20.02 (16.01, 27.19) nmol/L, P=0.376]. There were no significant differences in AACS and cardiac valve calcification score between the two groups before and after treatment. Gastrointestinal side effects such as nausea and vomiting were more common in lanthanum carbonate treated group (15.9% vs 1.6%, P=0.005). Conclusions Compared with sevelamer, lanthanum carbonate has a faster dephosphorization effect and higher initial serum phosphorus compliance rate, but the digestive tract tolerance is poor.