Background: The aim of this study was to compare the degradation resistance of nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) alloys used as a base material for partial dentures in contact with saliva. Methods: Wiron® 99 and Wironit Extra-Hard® were selected as representative casting alloys for Ni-Cr and Co-Cr alloys, respectively. The alloys were tested in contact with deionized water, artificial saliva and acidified artificial saliva. Material characterization was performed by X-ray diffractometry (XRD) and microhardness and nanohardness testing. The corrosion properties of the materials were then analyzed using open circuit potential analysis and potentiodynamic analysis. Alloy leaching in solution was assessed by inductively coupled plasma mass spectrometry techniques. Results: Co-Cr alloy was more stable than the Ni-Cr alloy in all solutions tested. Leaching of nickel and corrosion attack was higher in Ni-Cr alloy in artificial saliva compared with the acidified saliva. The corrosion resistance of the Co-Cr alloy was seen to be superior to that of the Ni-Cr alloy, with the former exhibiting a lower corrosion current in all test solutions. Microstructural topographical changes were observed for Ni-Cr alloy in contact with artificial saliva. The Ni-Cr alloy exhibited microstructural changes and lower corrosion resistance in artificial saliva. The acidic changes did not enhance the alloy degradation. Conclusions: Ni-Cr alloys are unstable in solution and leach nickel. Co-Cr alloys should be preferred for clinical use.