STATEMENT OF PROBLEM: Computer aided design/computer aided manufacturing (CAD/CAM) zirconia post-cores is one of the options of post crown restoration materials due to their esthetic properties and superior mechanical strength. However, the clinical effect on aesthetics and strength properties is unclear due to the lack of results of their long-term follow-up. PURPOSE: This retrospective clinical study aims to analyze the survival rate, clinical manifestations, and failure factors after CAD/CAM zirconia post-core restoration. MATERIAL AND METHODS: Clinical and radiographic examinations were performed on 342 patients with 400 teeth for 3-6 years postsurgical follow-up examination. The patients were all received CAD/CAM zirconia post-cores and all-ceramic crowns at the Department of Prosthodontics in the public hospital. The retrospective outcomes were conducted after zirconia post restoration, including survival rate by Kaplan-Meier analysis and findings of manifestations and failure factors. The effects of gender and dental position on survival rate were analyzed by Cox-Mantel Test. RESULTS: This study retrospectively evaluated 261 teeth from 229 patients with a 35% drop-out rate. The survival rate was 96.0%, and the success rate was 92.4%. According to the tooth position classification, the survival rate was 100% for 101 anterior teeth, 95.4% for 69 premolars, and 88.3% for 91 molars. According to gender, the survival rate of the male group was 92.3%, while that of the female group was 98.0%, with a significant difference (P < 0.01). The complications included crown fracture (1.9%) periapical inflammation (1.9%), crown debonding (1.1%), percussion abnormal (1.9%) and root fracture (0.8%). CONCLUSIONS: Within the limitations of this retrospective study, it can be concluded that CAD/CAM zirconia post-cores are clinically promising. Compared with the posterior teeth, CAD/CAM zirconia post-cores are more suitable for anterior teeth.