Objective. To evaluate the influence of sevelamer hydrochloride and calcium acetate on biomarkers of bone turnover in patients with hyperphosphatemia receiving hemodialysis. Methods. In this prospective, open-label, randomized, active-controlled study, 70 patients (38 men and 32 women) with hyperphosphatemia (serum phosphorus level >6.0 mg/dL) underwent a two-week washout period and were randomly selected to receive sevelamer hydrochloride (n = 37) or calcium acetate (n = 33) for eight weeks. Changes in serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (Alk-P), phosphorus, and calcium were measured and compared. Results. After eight weeks of treatment, calcium acetate lowered iPTH levels significantly more than sevelamer hydrochloride did (−178.0 vs. −69.0 pg/mL, p = 0.0019). Levels of Alk-P were significantly elevated in patients given sevelamer hydrochloride compared with levels in those given calcium acetate treatment (24.09 vs. 7.45 U/L, p = 0.0014). Changes in serum phosphorus levels did not differ between sevelamer hydrochloride (−1.93 mg/dL) and calcium acetate (−2.5 mg/dL) at the end of the study (p = 0.0514). Changes in the calcium and phosphorous product did not significantly differ between the sevelamer-hydrochloride group (−18.06 mg2/dL2) and the calcium-acetate group (−19.05 mg2/dL2, p = 0.6764). Fifteen patients (45.5%) treated with calcium acetate had hypercalcemia (serum-adjusted calcium level >10.5 mg/dL); the rate was significantly higher than that of patients treated with sevelamer (five [13.5%] of 37, p = 0.0039). Conclusion. Treatment with sevelamer hydrochloride had the advantage of maintaining stable iPTH levels and elevating Alk-P levels while lowering serum phosphorus levels and calcium-phosphorous product.