Purpose: This study evaluated the clinical performance of posterior CAD/CAM-generated In-Ceram Alumina and In-Ceram Spinell core crowns. Materials and Methods: Nineteen In- Ceram Spinell core crowns (four premolars and 15 molars) and 24 In-Ceram Alumina core crowns (two premolars and 22 molars) in 21 patients were examined using modified USPHS criteria at baseline and after a mean service time of 39 ± 11 months. The crown copings were machined from Vitablocs In-Ceram Alumina and Vitablocs In-Ceram Spinell using the Cerec 2 CAD/CAM system. Results: Two molar In-Ceram Alumina core crowns fractured after respective service times of 14 and 17 months in the same patient. The Kaplan-Meier survival rate regarding fracture of the ceramic was 92% for In-Ceram Alumina and 100% for In-Ceram Spinell. At the follow-up examination, 80% alpha ratings and 18% beta ratings for In-Ceram Alumina core crowns and 84% alpha ratings and 15% beta ratings for In-Ceram Spinell core crowns were recorded. Conclusion: Despite the two fractures, the clinical quality of CAD/CAM-generated In-Ceram Alumina and In-Ceram Spinell posterior crowns was excellent. Within the limitations of this study, both types of crowns appeared to be feasible.