Introduction: Dental health is of great concern to many patients and long-span edentulous spaces are difficult to be replaced with fixed prostheses, so removable partial dentures are still required. Aim: The purpose of this research was to compare between the effect of distal extension karadent and cobalt chromium (Co-Cr) removable partial denture frameworks on the supporting structures. Methods: Twelve male patients with bilateral mandibular distal extension ridge (last tooth is the 2nd premolar) opposing maxillary full set of dentitions were selected. According to the frameworks material used the patients were divided equally into two groups: The control group received a mandibular removable partial denture (RPD) made of cobalt chromium, while the test group received a mandibular RPD made of the thermoplastic semi-rigid microcrystalline polymer material (karadent). The data was recorded and statistically analyzed. Results: The results of this study showed that there were reduction in the alveolar bone width and height in both karadent and metal frameworks, but is higher in karadent. The differences between the two groups were statistically non-significant at (p≤0.05). Conclusion: Based on the limitations of this study, it could be concluded that the karadent frameworks recommended in distal extension RPD cases seeking for esthetics, but it has an adverse effect on the supporting bone in Kennedy Class I partially edentulous patients than cobalt chromium RPD.