Objectives: The aim of this prospective clinical study was to assess the long-term clinical survival rate and the technical and biological complication rates of zirconia-based posterior FDPs. Materials and Methods: Forty-five patients in need of one or more posterior FDPs received 57 three- to fiveunit zirconia-based FDPs. The frameworks were fabricated by means of a prototype computer-aided manufacturing (CAM) system (direct ceramic machining, DCM), first processing zirconia in the white stage. The frameworks were veneered with a prototype veneering ceramic. The FDPs were adhesively placed. At baseline, 6 months, and 1, 2, 3, 5, 8 and 10 years of function, the FDPs were examined for technical and/or biological complications. Furthermore, the periodontal health of the abutment teeth (test) and untreated control teeth was analyzed. Statistical analysis was performed applying descriptive statistics, Kaplan-Meier survival and multiple mixed effects regression tests. Results: Twenty-one patients with 26 FDPs were examined at a mean observation time of 10.7 ± 1.3 years. A total of 16 FDPs were lost to follow-up. Fifteen FDPs had to be replaced due to technical/biological complications; hence, the 10-year survival rate of the FDPs was 67%. Three framework fractures occurred, resulting in a 10-year survival rate for the zirconia frameworks of 91.5%. Chipping/fracture of the veneering ceramic was detected in 16 FDPs over 10 years (complication rate 32%). A significant correlation of the span of the FDPs and the incidence of chipping was observed: 4- and 5-unit FDPs had a 4.9 times higher probability for chipping than 3-unit FDPs. Marginal discrepancy/degradation was found in 90.7% of the FDPs over 10 years. At 11 of the FDPs (complication rate 27%), secondary caries occurred. No difference of the periodontal health was found around test and control teeth. Conclusion: The zirconia frameworks exhibited very good long-term stability. However, the zirconia-based FDPs frequently exhibited problems such as marginal deficiency or chipping of the veneering ceramic. Both problems may be associated with the prototype status of the system. Keywords: zirconia, framework, fracture, long-term, FDP, chipping, marginal adaptation