This study aimed to assess the effect of Nickel-containing metallic restorations on liver and kidney blood tests. Methods: Twenty patients were selected from the Fixed Prosthodontics clinic, Faculty of Dentistry, Tanta University, to be included in this study. Ten patients who never had metallic restorations were studied as a control group (group I). The other group included 10 patients with old porcelain fused to metal (PFM) or metallic restorations (group II). Liver, kidney, and serum Nickel (Ni) level tests were measured for all at the beginning of the study. For group II patients, the metallic restorations were replaced with Zirconia then liver, kidney, and serum Ni level tests were repeated six months after insertion of the new restorations. Results: At the beginning of the study, liver and kidney tests were significantly worse in patients of group II than in group I. But, there was no significant difference as regards blood cell counts between both groups. Six months after replacement with Zirconia restorations for group II patients, there was a significant improvement in their liver and kidney function tests, a decrease in WBCs count, and a slight increase in hemoglobin level than baseline. Also, the serum Nickel test significantly dropped after the replacement of metallic restorations. Conclusion: within the limitations of this study, Nickel released from metallic restorations has a negative impact on liver and kidney blood tests, especially those with multiple restorations or prolonged durations