ObjectivesTo compare volumetric wear of lithium disilicate against different ceramic (3 mol% yttria‐stabilized (3Y) zirconia, 5 mol% yttria‐stabilized (5Y) zirconia, lithium disilicate, porcelain and enamel antagonists).Materials and MethodsForty lithium disilicate (e.max CAD) specimens (n = 8/antagonist) were wet sanded to 1200grit SiC and mounted into a UAB wear device. Antagonist spheres (diameter = 4.75 mm) were made from polished 3Y zirconia, 5Y zirconia, lithium disilicate, porcelain and human enamel. A two‐body wear test was performed with 20 N load and 1.5 mm slide for 400,000 cycles at 1 Hz. 33% glycerin was used as a lubricant. Wear facets were measured with optical profilometry. Wear scar areas of antagonists were measured with digital microscopy. Scanning electron microscopy was performed on wear facets and scars. Vicker's microhardness was measured of all antagonist materials. All data were compared with 1‐way ANOVA and Tukey post‐hoc analysis.ResultsSignificant differences in lithium disilicate volumetric wear (mm3) occurred with various antagonist materials: 0.38 ± 0.01a (3Y zirconia), 0.33 ± 0.01b, (5Y zirconia), 0.16 ± 0.01c (lithium disilicate), 0.11 ± 0.03d, (enamel), and 0.07 ± 0.01e (porcelain). The lithium disilicate antagonist demonstrated a larger wear scar than other materials. Zirconia was the hardest material and enamel the least hard.ConclusionsZirconia causes significant wear on lithium disilicate and lithium disilicate causes significant wear against itself.Clinical SignificanceWhen selecting a material to oppose an existing lithium disilicate crown, a porcelain or lithium disilicate surface would cause significantly less wear to the existing crown. If an existing zirconia crown exists opposed to a prepared tooth, lithium disilicate may not be an ideal material selection to restore the tooth.