Background Wear and quality assessments of translucent monolithic zirconia and CAD-on(R) restorations were performed. Methods Forty 3-unit posterior fixed partial denture (FPD) in 18 patients (age:18-50 years) were made from translucent monolithic zirconia (tm) (Zenostar T) and zirconia-frameworked, lithium disilicate layered (c) (CAD-on), materials in a split-mouth design. Restorations were digitally fabricated and their internal and marginal adaptations were measured before cementation followed by luting (Multilink Speed). Clinical evaluations were made by modified United States Public Health Service criteria at baseline, 6, 12, and 24-months. Wear of the restorations and the antagonists were digitally evaluated after optical scanning of stone casts at 1st week and 24 m through a software (Cerec 4.4). Statistical analysis was made (analysis of variance, Shapiro-Wilk, Friedman and Wilcoxon tests (SPSS 20)) at alpha = 0.05 significance level. Results At 24 m, all restorations were clinically acceptable. Insignificant differences were found between tm and c restorations (P > 0.05). Mean internal and marginal adaptation of c restorations were significantly better (145 mu m (premolar)-174 mu m (molar)) than tm (190 mu m (premolar)-207 mu m (molar)) (P < 0.05). C restorations significantly caused more wear (0.3 +/- 0.1 mm) than tm (0.1 +/- 0.07 mm) on the antagonistic dentition (P < 0.05). Conclusions Translucent monolithic zirconia restorations caused less wear and antagonist wear than CAD-on restorations. CAD-on restorations exhibited higher internal and marginal adaptation.