Objectives: To assess the effect of a CAD-CAM protocol fabrication on the clinical fit accuracy of removable partial denture metal frameworks to abutment teeth. Methods: Fifteen patients with partial edentulism were selected to participate in this clinical study, and twenty dental arch rehabilitations were planned. For each dental arch (n=20), two cobalt-chromium frameworks were produced through two protocols: CAD-CAM production (experimental group); and conventional lost-wax casting technique (control group). Clinical fit accuracy was assessed using an indirect quantitative method to evaluate the gap between the framework occlusal rest and the corresponding rest seat. A silicone mold of that gap was obtained, digitized, and analyzed by micro-computed tomography. The two silicone molds obtained for each occlusal rest were overlapped and evaluated for thickness and volume. Data were analyzed with the paired t test for silicone thickness results and the Wilcoxon test for silicone volume results (α= 0.05). Results: Considering the two dependent variables under study, no statistically significant (p=0.441 for silicone thickness and p=0.204 for silicone volume) differences were found between groups. Conclusions: The results of this study suggest that the CAD-CAM protocol applied is a viable method for the production of removable partial denture metal frameworks. (Rev Port Estomatol Med Dent Cir Maxilofac. 2021;62