© 2021 Editorial Council for the Journal of Prosthetic DentistryStatement of problem: The wear of monolithic zirconia against enamel has been widely studied, but how zirconia affects different opposing restorative materials is not clear. Purpose: The purpose of this in vitro study was to investigate the depth of wear and volumetric loss of different restorative materials opposed by monolithic zirconia. Material and methods: Sixty-six Ø10×3-mm specimens (n=11) were fabricated from monolithic zirconia, zirconia reinforced ceramic, lithium disilicate ceramic, feldspathic ceramic, ORMOCER, and ceramic optimized polymer. A 2-body pin-on-disk wear test was performed by using monolithic zirconia pins. The specimens were scanned with a noncontact profilometer after the tests. The scan parameters were a frame size area of 1.5×1.5 mm, frequency of 400 Hz, and scan sensitivity of 2 μm. After the evaluation of depth and volume loss, the specimens were analyzed with a scanning electron microscope. The Kruskal-Wallis test was used to analyze the differences in wear values across the specimen groups, and pairwise comparison tests were performed with a post hoc test (α=.05). Results: Maximum depth of wear was 257.55 ±18.88 μm for lithium disilicate ceramic, 295.36 ±14.46 μm for zirconia reinforced ceramic, 421.82 ±214.49 μm for ORMOCER, 333.73 ±79.09 μm for ceramic optimized polymer, 146.27 ±22.86 μm for feldspathic ceramic, and 41.55 ±5.04 μm for monolithic zirconia. The depth of wear was not significantly different among lithium disilicate, zirconia-reinforced ceramic, ORMOCER, and ceramic optimized polymer (P<.05). However, the depth of wear of monolithic zirconia and feldspathic ceramic was less than that of other materials (P<.001). Volume loss of lithium disilicate was 1.68 ±0.25 mm3, 1.08 ±0.35 mm3 for zirconia reinforced ceramic, 4.29 ±2.91 mm3 for ORMOCER, 2.46 ±0.63 mm3 for resin ceramic, 1.07 ±0.09 mm3 for feldspathic ceramic, and 0.19 ±0.02 mm3 for monolithic zirconia. Feldspathic ceramic and monolithic zirconia had significantly less volume loss than the other groups (P<.001), and the difference between them for volume loss was statistically insignificant (P>.05). Conclusions: The tested ceramic-based materials had favorable wear resistance compared with the tested composite resin–based ones. However, the ceramics tended to crack formation than the composite resins.