Statement of problem: Hot-pressing and computer-aided design and computer-aided manufacturing (CAD-CAM) are major techniques for the fabrication of lithium disilicate crowns. They exhibit different accuracies regarding marginal fit, an important factor in restoration survival. However, studies comparing the marginal fit of different fabrication methods are lacking. Purpose: The purpose of this in vitro study was to compare the marginal discrepancy (MD) and absolute marginal discrepancy (AMD) of lithium disilicate crowns produced by the hot-press and CAD-CAM techniques. Material and Methods: Thirty typodont teeth were divided into 2 groups. Fifteen teeth were scanned with the CEREC Omnicam intraoral scanner, and crowns were fabricated with the CEREC MC XL chairside CAD-CAM milling unit from IPS e.max CAD blocks. Fifteen typodont teeth were sent to a dental laboratory, and lithium disilicate crowns were fabricated from IPS e.max press ingots using the hot-press technique. The 30 crowns were cemented and then sectioned with a precision saw. The MD and AMD were measured for each crown with a light microscope. One-way ANOVA was conducted to analyze significant differences in crown marginal fit between the fabrication systems (α=.05). Results: For the CAD-CAM technique, the mean values of the AMD measurements were 115 μm, and for the hot-press technique, 130 μm. The MD measurements were 87 μm for the CAD-CAM technique and 90 μm for the hot-press technique. One-way ANOVA revealed no significant differences between the fabrication methods regarding marginal fit (P>.05). Conclusions: No significant differences were found between the fabrication methods tested. Both the CAD-CAM and hot-press techniques for producing monolithic lithium disilicate crowns produced MD values of less than 120 μm, within the clinically acceptable range.