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The selection of an appropriate restorative material based on wear behavior is important for the long-term success of a dental restoration. For computer-aided design and computer-aided manufacturing (CAD-CAM) composite resins, information about their wear resistance and wear mechanism is scarce.The purpose of this in vitro study was to compare the 2- and 3-body wear of CAD-CAM composite resins with that of lithium disilicate ceramic and to develop analysis software.Flat specimens were prepared from the following CAD-CAM composite resins: Cerasmart (CS), SHOFU Block HC (SH), Katana Avencia (KA), Brilliant Crios (BC), an experimental composite resin (EXP), and lithium disilicate ceramic IPS e.max CAD (REF). The specimens underwent 2-body wear (50 N, 5/55°C, 400 000 cycles) opposed by human enamel antagonists. Specimen wheels were prepared with each material on each wheel for 3-body wear with a millet slurry (15 N, 15% slip, 200 000 cycles). All specimens were digitized by using a dedicated laser scanner. Analysis software was developed to calculate macrotopographical examination of volume loss. The microtopography of the surfaces was examined by using scanning electron microscopy. For data analysis, the Kruskal-Wallis test with the Tukey-Kramer post hoc test and the 1-sample Wilcoxon test were used (α=.05).After 2-body wear simulation, SH and KA presented higher volume loss than the other CAD-CAM materials. For 3-body wear, REF had lower volume loss than CS, SH, or BC. In addition, BC led to higher volume loss than EXP. The patterns of 2- and 3-body wear were different.The ceramic showed good global wear resistance. The volume loss of the CAD-CAM composite resins differed and depended on the material. The 2- and 3-body wear test methods tended to differ with regard to volume loss. Examination of the worn surfaces revealed different mechanisms acting in 2- and 3-body wear test.