This in vitro study performed a two-body wear test on four different chair-side CAD/CAM ceramic materials. The study aimed to compare wear resistance between three lithium disilicate and one zirconia reinforced lithium silicate CAD/CAM material, in terms of the volume loss. Six flat square specimens (8 x8 x4 mm3) were prepared from each IPS emax CAD (EM), n!ce (NI), Amber Mill (AM), and Celtra Duo (CD) CAD/CAM blocks. Only EM and AM specimens were crystallized using a furnace following the manufacturers’ instructions. Spherical steatite ceramic with a diameter of 6 mm was used as an antagonist. The specimens and antagonists were embedded in the wear simulation holder using auto-polymerized acrylic resin to secure the specimen and stored in deionized water at 37oC for 7 days before wear testing. The simulated two-body wear was performed using a chewing simulator (120,000 cycles, 50 N, 1.34 Hz, sliding movement 0.5 mm). The volume loss of the specimen was measured after 120,000 cycles using a contact profilometer. The height loss of the antagonist opponent was measured using a stereomicroscope and the volumetric loss was calculated. Data were analyzed with one-way ANOVA, followed by Tukey or Games-Howell post-hoc analysis (α = 0.05). The highest specimen volume loss was EM (0.51±0.10 mm3), followed by CD (0.48±0.06 mm3), NI (0.27±0.03 mm3), and AM (0.10±0.02 mm3), respectively. The result of statistical analysis in volume loss showed significant differences among materials (p <0.001). Post hoc analysis revealed that EM demonstrated a significantly greater volume loss than AM and NI (p <0.05) but showed comparable to CD (p >0.05). For the steatite antagonist, the steatites opposed to NI demonstrated the least antagonist volume loss compared to the others (p <0.05). The wear behaviors and wear resistance of glass-ceramics were influenced by their mechanical properties and microstructure, such as crystal size and crystal volume fraction. New lithium-based glass-ceramic materials, especially n!ce, showed better wear resistance and caused less abrasion to antagonists when compared with IPS emax CAD.