OBJECTIVE The objective of this study was to evaluate the clinical performance of zirconia-based all-ceramic fixed partial dentures anchored by inlays. METHODS A total of thirty FPDs, manufactured using a zirconia frame and veneered with press ceramic, were anchored by use of inlay retainers. All FPDs were designed to replace one missing molar and were adhesively luted by use of one of two different resin cements. Documentation included failures and other complications, plaque accumulation, and aesthetic and functional performance. Statistical analysis was performed using a cox-regression model. RESULTS During the 12 months observation period a total of thirteen clinically relevant complications occurred-four delaminations of the veneer and six decementations. Three FPDs had to be replaced because of a fracture of the framework. The cement chosen, the location, and the design of the retainer had no statistically significant effect on the occurrence of complications. During the observation period, accumulation of plaque on the abutment teeth was not significantly greater than on reference teeth. Postoperative sensitivity did not differ significantly between the different luting cement groups. The aesthetic and functional performance of the FPDs was acceptable. CONCLUSIONS Improved adhesion between resin cement and inlay retainer is desirable before general recommendation of all-ceramic inlay-retained FPDs. Use of different luting cements seems to have no effect on the occurrence of complications.