Background: Cardiovascular disease is the main cause of death in patients with end stage renal disease. Fibroblastic growth factor- 23 (FGF-23) is a novel phosphaturic hormone produced in the osteocyte. Patients with kidney disease complain of elevated levels of FGF-23 in response to hyperphosphatemia. Patients and Methods: This was a cross-over prospective study conducted on 30 patients on regular hemodialysis. The study period was 6 months, laboratory investigations for FGF-23, complete blood picture, s. urea (pre-dialysis and post-dialysis), serum albumin, serum electrolytes (Ca++ & PO4), alkaline phosphatase, PTH, serum ferritin, and lipid profile as well as echocardiography were obtained in the start of the study, after 3 months on maintained lowflux hemodialysis and 3 months after switching the patients to high-flux hemodialysis. Results: There was a highly significant reduction of FGF-23 level with high-flux dialyzers than with low-flux dialyzers. The adjusted difference in the absolute change in FGF-23 levels between the three months period of lowflux dialysis and the three months period of high-flux dialysis showed a highly significant reduction with high-flux than with low-flux (p= 0.000). There was a significant reduction of serum levels of PTH, calcium, phosphorus levels with high-flux dialyzers than with low-flux dialyzers, the adjusted difference was (p= 0.022), (p= 0.000), and (p= 0.006) respectively. Conclusion: FGF-23 levels were significantly higher in hemodialysis patients than in normal population. FGF-23 was better eliminated by high-flux dialyzers than low-flux dialyzers and high FGF-23 levels were associated with increased incidence of cardiac valve calcification. FGF-23 positively correlated with right ventricular systolic pressure.