Background <p>A lot of studies have demonstrated the increased hardness of the reinforced maxillary dentures. However, the amount of stress induced by different reinforcement materials under the reinforcement dentures and their effect on the underlying supporting tissues and on the deformation of the denture bases were questionable. This study was conducted to compare the stresses induced within the supporting oral tissues from maxillary denture bases reinforced with computer-aided designing/computer-aided manufacturing CAD/CAM zirconia framework or cobalt chrome (Co-Cr) framework, and to detect the deformation that occurred to these bases. </p> Materials and methods <p>Twenty-six maxillary complete dentures were fabricated and divided into two groups (n = 13). Group A (test group): zirconia framework reinforcement. Group B (control group): Co-Cr framework reinforcement. All denture bases were subjected to unilateral static loading, and then the strain was monitored using a strain gauge analysis device. Then the reinforced denture bases of both groups were subjected to dynamic cyclic loading, then deformation was detected using Geomagic software. </p> Results <p>Group A; showed significantly higher strain measured at all measuring areas compared to Group B. The maximum principal strain (MPS) at the 1st right molar area was consistently the highest among all measuring areas, regardless of the denture reinforcement framework type. Deformation results suggested that Group A; showed statistically significant reduced deformation compared to Group B after dynamic cyclic load application.</p> Conclusion <p>Zirconia framework-reinforced maxillary dentures were associated with higher strains and less framework deformation than cobalt chrome framework-reinforced maxillary dentures when static and dynamic loading were applied.</p>