Clinical studies on the behavior of posterior translucent monolithic zirconia restorations are lacking. We assessed the clinical outcome and survival rate of posterior third-generation monolithic zirconia crowns over a 2-year period. A total of 24 patients, requiring 30 posterior full-contour restorations were selected. All abutments were scanned, and crowns were milled and cemented with a self-adhesive dual cure cement. Crowns were assessed using the California Dental Association’s criteria. Gingival status was assessed by evaluating the gingival index, plaque index, periodontal probing depth of the abutments and control teeth, and the margin index of the abutment teeth. Statistical analyses were performed using the Friedman and the Wilcoxon signed-rank tests. During the 2-year follow-up, no biological or mechanical complications were observed, and the survival and success rate was 100%. All restorations ranked as satisfactory throughout the follow-up period. The gingival index and plaque index were worse at the end of the 2-year follow-up. The margin index was stable during the 2 years of clinical service. No significant differences were recorded in periodontal parameters between crowns and control teeth. Third-generation monolithic zirconia could be a reliable alternative to posterior metal–ceramic and second-generation monolithic zirconia posterior crowns.