This systematic review and meta-analysis aimed to investigate the accuracy of removable partial denture (RPD) frameworks fabricated by computer-aided design/ computer-aided manufacturing (CAD/CAM) systems compared to frameworks produced by conventional casting methods. A systematic literature search was conducted in electronic databases following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, using formulated Boolean operator for searching articles evaluating the fit accuracy of CAD/CAM-fabricated RPD metal frameworks. The agreement of data collection among the reviewers was confirmed using the Cohen kappa coefficient. The modified methodological index for non-randomized studies (MINORS) scale was used to assess the quality of the included studies. Heterogeneity among studies was evaluated, and meta-analyses with global and subgroup analyses were performed. A total of 208 articles were identified with 18 articles available for the narrative review and 7 studies available for meta-analysis on the 3D-printed frameworks for RPD (the overall Cohen kappa coefficient = 0.944). There was no article on the accuracy of RPD frameworks made by milling method. The meta-analysis revealed that the misfit of frameworks obtained with the CAD/CAM method was significantly higher than that of the conventional lost wax and casting method (SMD = 1.23 μm, 95% CI = 0.3610-2.0981 μm, z = 2.77, P = .0055). Regarding the CAD/CAM techniques used for fabricating RPD metal frameworks, the within subgroup analysis showed that the CAD/CAM-based indirect fabrication method produced frameworks with fit accuracy more similar to the conventional lost-wax and casting method (SMD = 1.15 μm, 95% CI = - 0.06136-2.9192 μm, z = 1.28, P < .01) than the CAD/CAM-based direct fabrication method (SMD = 1.35 μm, 95% CI = -0.2722-2.4381 μm, z = 2.45, P < .01), even though there was no statistical difference between the techniques (P = .8482). The fit accuracy of RPD metal frameworks fabricated by the CAD/CAM method was lower than that of frameworks fabricated by the conventional casting method, but it was within the clinically acceptable range in dimensional misfit. The indirect metal 3D printing technique based on pattern printing and subsequent casting produced frameworks with fit accuracy more similar to the conventional method than the direct fabrication technique.