© 2022 Editorial Council for The Journal of Prosthetic DentistryStatement of problem: Dental ceramics have been reported to elute ions when subjected to nonneutral pH. However, the effect of surface treatments and thermomechanical aging on the ion elution of CAD-CAM ceramics is unclear. Purpose: The purpose of this in vitro study was to compare the effect of surface treatment (glazed or polished) and thermomechanical aging on the ion elution of CAD-CAM materials before and after 2-body wear simulation. Material and methods: Specimens were prepared from 6 CAD-CAM materials—leucite (LC), feldspathic (FP), zirconia-reinforced lithium silicate (ZLS), lithium disilicate (LDS) glass-ceramics, polymer-infiltrated ceramic network (PICN), and zirconia (ZIR)—and divided into 2 groups according to the surface treatments (glazed or polished) (n=6). For baseline ion elution values, specimens were placed into polyethylene bottles containing deionized water (pH 7.4) that had been stored in an incubator for 168 hours at 37 °C. The eluted ions in the immersion solution were measured by using inductively coupled plasma-optic emission spectrophotometry. The specimens were then subjected to thermomechanical aging by using human enamel as an antagonist. After aging, the ion elution of the specimens was remeasured. Ion elution data before and after 2-body wear were analyzed by using the Mann-Whitney U test, while the effect of 2-body wear was assessed by using the Wilcoxon signed rank test (α=.05). Results: The presence of some ions varied depending on the material-surface treatment pair before (Al, As, B, Ba, Ca, K, Li, Mg, Na, P, and Zn) and after (Al, B, Ba, Ca, Co, Li, Mg, and P) 2-body wear. Polished materials had higher ion elution than the glazed materials before 2-body wear (P≤.041), except for LC (P and Zn) and PICN (Ca, Cu, and K) (P≤.009). After 2-body wear, polished LC (B and Ba), FP (Al, B, and Mg), ZLS (Al, Ba, Ca, and Li), ZIR (B and Ba), glazed PICN (Ca, Mg, and P), ZLS (P), and ZIR (Co) presented higher ion elution than their counterparts (P≤.041). The effect of 2-body wear on the ion elution of polished LC (Al, K), FP (Na), ZLS (Li), LDS (K, Na), PICN (Al, Na), ZIR (Na, Y), glazed LC (Na), FP (Ba, Na), ZLS (B, Ba, Y), LDS (Na), PICN (Y), and ZIR (Na) was nonsignificant (P≥.075). However, the elution of remaining ions showed a significant difference before and after 2-body wear (P≤.046). Conclusions: The chemical stability of tested CAD-CAM materials was affected by the 2-body wear. Glazing led to a lower ion elution except for LDS and PICN. While polishing resulted in lower ion elution for PICN, both surface treatments resulted in similar ion elution for LDS.