This study aimed to compare the retention force between CAD-CAM milled PEEK versus CAD-CAM milled Acetal resin RPDs and the conventionally constructed Co-Cr removable partial dentures (RPD) used as a control group . Material and methods: Thirty patients with mandibular class I Kennedy were selected, all the patient had bilateral lower first premolars as last remaining abutments. Each patient received three types of removable partial dentures; Conventional (Co-Cr) RPDs, CAD-CAM milled poly-oxy-methylene (Acetal Resin) and CAD-CAM milled poly-ether-ether-ketone, (PEEK) RPDs, the patients were instructed to underwent a rest period for two weeks before they were delivered the other type of RPD. The retention was measured at the time of insertion as a baseline and after three months from delivery. Results: The retention forces in the conventional (Co-Cr) group were higher than that of CAD-CAM milled PEEK and milled Acetal RPDs engaging the same undercuts. There was a high significant difference in the retention force between CAD-CAM milled (Acetal and PEEK), and Co-Cr RPDs in favor of Co-Cr RPDs, and a significant difference between CAD-CAM milled Acetal and milled PEEK RPDs in favor of milled Acetal. Conclusions: Within the limitations of this study, it can be concluded that, the use of CAD-CAM technology can be a promising alternative to conventional technique. Although metallic prosthesis showed higher retention values, recent CAD-CAM technology by milling polymeric materials (Acetal and BEEK) exhibited sufficient retention to recommend usage under some clinical conditions; as when aesthetic demand or periodontal health is a primary concern.