Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m 2 to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain. CKD is a significant public health concern; roughly 13% of the US population has an estimated GFR (eGFR) below 60 ml/min per 1.73 m 2 or albuminuria. 1 The risks of death and cardiovascular disease in CKD are not fully explained by associated diabetes, hypertension, and other conventional risk factors. 2 With declining kidney function, serum phosphorus concentration increases but generally remains within the normal range until late in stage 4 or 5 CKD. A normal or near-normal serum phosphorus concentration is maintained at the expense of elevated levels of the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). 3,4 Serum concentrations of phosphorus and hormones responsible for its regulation have been implicated as putative cardiovascular risk factors. [5][6][7][8][9]