Purpose: The aim of this in vitro study was to compare the internal 3D adaptation of polymer-infused ceramic crowns fabricated using two CAD/CAM systems: CEREC inLab MC XL and Ceramill Motion 2 (5X). Materials and Methods: Twenty-five implant-supported metal-ceramic crowns were fabricated conventionally using the lost-wax technique, and the outer contour was scanned to serve as a guide for designing the polymer-infused ceramic CAD/CAM crowns. Twenty-five crowns were fabricated using CEREC, and 25 crowns were fabricated using Ceramill. The cement space was set to 20 μm. The Zeiss Accura Microsystem Coordinate Measuring Machine (CMM), Calypso, and Geomagic software were used to measure the 3D accuracy of fit of all crowns to their respective implant abutments. To test for the statistical significance between groups in terms of 3D total distortion, a one-way ANOVA was conducted. The Kolmogorov-Smirnov test was used to investigate the differences in the x, y, and z coordinates. A p-value of 0.05 or less was considered statistically significant at an alpha level of 0.05. Results: Comparing the 3D misfit of metal-ceramic crowns to those of CAD/CAM crowns fabricated using CEREC revealed no significant difference (88.20 ± 36.59 μm vs. 102.45 ± 36.58 μm, p = 0.161). Similarly, no significant difference in 3D total distortion was identified between metal-ceramic crowns and crowns fabricated using Ceramill (88.20 ± 36.59 μm vs. 78.40 ± 31.03 μm, p = 0.336); however, the 3D total distortion of polymer-infused crowns made by Ceramill was significantly reduced compared to that of crowns fabricated by CEREC (78.3 ± 31.0 μm vs. 102.4 ± 36.5 μm, p = 0.019). Conclusions: Polymer-infused ceramic crowns fabricated using CEREC exhibited the least accurate 3D fit. All misfit values of the tested groups were within clinically acceptable levels.