STATEMENT OF PROBLEM: Monolithic zirconia crowns fabricated with computer-aided design and computer-aided manufacturing (CAD-CAM) have recently become a common practice for the restoration of posterior teeth. The marginal fit of monolithic zirconia crowns may be affected by different cement space parameters set in the CAD software. Information is scarce regarding the effect of cement space on the marginal fit of monolithic zirconia crowns fabricated with CAD-CAM technology. PURPOSE: The purpose of this in vitro study was to evaluate the effect of cement space on the marginal fit of CAD-CAM-fabricated monolithic zirconia crowns before cementation. MATERIAL AND METHODS: Fifteen right maxillary first molar typodont teeth with standardized anatomic preparations for complete-coverage ceramic crowns were scanned with a 3-dimensional laboratory scanner. Crowns were designed 3-dimensionally using software and then milled from presintered monolithic zirconia blocks in a computer numerical control dental milling machine. The cement space was set at 25 μm around the margins for all groups, and additional cement space starting 1 mm above the finish lines of the teeth was set at 30 μm for group 25-30, 40 μm for group 25-40, and 50 μm for group 25-50 in the CAD software. A total of 120 images (3 groups, 5 crowns per group, 8 sites per crown) were measured for vertical marginal discrepancy under a stereoscopic zoom microscope and the data were statistically analyzed with 1-way analysis of variance, followed by the Tukey honestly significant difference test (α=.05). RESULTS: The results showed that different cement space values had statistically significant effect on the mean vertical marginal discrepancy value of tested crowns (P<.001). The mean marginal discrepancy was 85 μm for group 25-30, 68 μm for group 25-40, and 53 μm for group 25-50. CONCLUSIONS: Within the limitations of this in vitro study, it was concluded that the cement space had a significant effect on the marginal fit of CAD-CAM-fabricated monolithic zirconia crowns. The marginal fit improved as the cement space decreased.