Clinical Relevance Marginal misfit of monolithic lithium disilicate ceramic crowns obtained from a chairside computer-aided design/computer-aided manufacturing system is affected after successive millings using a single diamond bur set. This fact can be critical for the longevity of indirect restorations. SUMMARY Objectives: This laboratory study aimed to assess the effect of successive crown millings on the marginal misfit of monolithic full-ceramic restorations obtained from two lithium disilicate systems, with a single diamond bur set used for each material in a chairside computer-aided design/computer-aided manufacturing (CAD/CAM) unit. Methods and Materials: Initially, 36 standardized composite resin dies were produced by additive manufacturing from a three-dimensional model of a right mandibular first molar with full-crown preparation generated in CAD software. Individual ceramic crowns were obtained in a chairside CAD/CAM unit (CEREC MC XL) for each composite resin die according to the ceramic system (IPS e.max CAD and Rosetta SM; n=18). Two new diamond burs were used as a set for obtaining the crowns in each experimental group (ceramic systems), and the milling periods were defined after three crown millings (T0-T6), when the diamond bur set of each system was removed for morphologic characterization using scanning electron microscopy (SEM). The marginal misfit of the crowns was assessed through coronal and sagittal micro-tomographic sectioning, in the vertical and horizontal directions of the ceramic crowns seated on their respective resin dies. The collected data were tabulated and subjected to one-way analysis of variance and Tukey's honestly significant difference test (α=0.05). Results: SEM images showed changes in the superficial morphology of the diamond bur sets, with progressive loss of the diamond granules after the successive millings of crowns for both experimental groups. Significant differences were detected in the marginal misfit of the crowns from both ceramic systems at the different milling periods ( p <0.001). Conclusions: Diamond burs deteriorated after successive crown millings for both lithium disilicate ceramic systems. The marginal misfit of the crowns obtained increased with the successive use of the CAD/CAM diamond bur set employed for milling each ceramic material. In addition, new milling of full lithium disilicate ceramic crowns can be inappropriate after 11 successive millings for IPS e.max CAD and 12 for Rosetta SM, due to the increased marginal misfit observed under the parameters tested.