Purpose: To evaluate the marginal accuracy of soft-milled cobalt-chromium (Co-Cr) compared to other construction methods/restorative materials in tooth/implant-supported restorations. Materials and Methods: PICO questions were defined, and a systematic search was conducted in six electronic databases. Titles and abstracts were collected and screened by two independent reviewers. After removing duplicate articles, the full texts of relevant articles were gathered, and the required information and data were extracted. Risk of bias was assessed and meta-analyses of the collected data were conducted using STATA software version 16. Results: A total of 1,914 experimental and clinical articles were reviewed, and 18 studies were selected for qualitative analysis. The 16 studies that were included in the meta-analysis showed no significant marginal gap differences between soft-milled Co-Cr and the following methods/materials: hard-milled Co-Cr (I2 = 92.9%, P = .86), casting wax (I2 = 90.9%, P = .42), laser-sintered Co-Cr (I2 = 93.3%, P = .46), and zirconia (I2 = 0.00%, P = .47). However, a significantly higher marginal accuracy of soft-milled Co-Cr was observed when compared to milled-wax casting (I2 = 93.1%, P < .001). Conclusion: The marginal gap of soft-milled Co-Cr restorations is within the acceptable clinical range and provides an accuracy similar to other available methods/materials for both the prepared implant abutment and tooth.