There was some worry about an increase in the risk of vascular calcification when calcium-based phosphorus binders were used. The study sought to compare the effects of sevelamer as a second-line, low-dose therapy with calcium-phosphorus binders with those of sevelamer as a first-line, high-dose therapy on coronary artery and heart valve calcification, aortic pulse wave velocity (PWV), and calcification propensity in patients receiving patients with hyperphosphatemia at two university-affiliated hospitals in Hong Kong were included. The patients were assigned to receive sevelamer as first-line therapy at a high dose of 800 mg 3 times daily (can be titrated up to 1,200 mg 3 times daily if required) or a second-line therapy at a low dose of 400 mg 3 times daily with calcium carbonate to reach an adjusted serum phosphate concentration goal. The primary endpoints were coronary artery calcium score changes and aortic PWV over 104 weeks. The second set of endpoints was a 104-week improvement in heart valve calcium scores, calcification propensity measure, and biochemical markers of chronic kidney disease–mineral bone disease. In 60 prevalent patients receiving PD, with a mean age of somewhere between 53 and 10 years and with 57% men, changes in the coronary artery calcium score (median [interquartile range], 225 [79-525] vs 223 [56-1,212], respectively; P=0.21), aortic PWV (mean ± standard error, 0.3±0.1 vs 0.8±0.2 m/s, respectively; P=0.31). The second-line, low-dose, and first-line, high-dose sevelamer groups had similar changes in the maturation or transformation rate (1.6%), calcium score (1.9%), serum calcium levels (0.7%), and phosphorus levels at 104 weeks. Both groups showed a significant decrease in low-density lipoprotein cholesterol, and both were treated with simvastatin. Both the control and experimental groups demonstrated increased alkaline phosphatase levels (no significance between the groups). Low-dose sevelamer as second-line therapy for hyperphosphatemia combined with calcium-based phosphorus binders had comparable effects on vascular calcification, valvular calcification, and arterial stiffness to high-dose sevelamer as first-line therapy. The method might have been considered to minimize calcium loading in countries with a scarcity of resources.