OBJECTIVES: Assessment the safety and the efficacy of nicotinamide as adjunctive therapy to calcium carbonate (as phosphate binder). METHODS: Study design and setting: A prospective, interventional, open-labeled, case control randomized trial was performed at Ain Shams University Specialized Hospital and Al Motamayz hemodialysis center, Cairo, Egypt, from August 2010 to December 2010. Patients and Methods: Sixty hemodialysis patients with serum phosphorus level ≥ 5.0 mg/dl were classified into two groups; group I (control group) in which patients received calcium carbonate tablets in dose of 500mg to 1000mg three t.i.d. And group II (study group) in which patients received calcium carbonate in dose of 500mg to 1000mg t.i.d. and nicotinamide tablets in a dose titrated to 1000mg/day for 8 weeks. Serum calcium, phosphorus and intact parathyroid hormone were measured at week 1 and 9 to assess the efficacy of treatment. RESULTS: Fifty-six patients successfully completed the trail. Serum phosphorus level falls significantly from 6.75 to 5.47 mg/dl with group II and not with group I (from 6.46 to 6.53 mg/dl). A concurrent fall in calcium- phosphorus product was seen with nicotinamide treatment (from 58.7 to 48.55 mg2/dl2), whereas serum calcium, intact parathyroid hormone, uric acid, platelet count, total cholesterol, hemoglobin, AST, and ALT remained stable in both arms. A trend toward increasing HDL and reducing LDL and triglycerides were reported in nicotinamide group however the overall changes were statistically non significant. Diarrhea and other gastrointestinal disturbances symptoms were the major adverse effects seen with nicotinamide treatment. CONCLUSIONS: Nicotinamide in single dose of 1000 mg daily can effectively reduce serum phosphorus level when administered with calcium carbonate (as phosphate binder) with less potential side effects.