Purpose: In this prospective clinical study, the performance of three- and four-unit fixed partial dentures (FPDs) with frameworks fabricated of yttria partially stabilized zirconia was determined after a mean observation period of 50 months. The study focused on the survival of the restoration (in situ criterion) and the success of the ceramic veneers (no defect). Materials and Methods: Seventy-five patients with a maximum of two missing teeth and an antagonistic dentition were treated at the Department of Prosthodontics, University of Goettigen, with 99 posterior FPDs. Fiftyone specimens (experimental group) were veneered with an experimental ceramic suitable for titanium and zirconia frameworks (thermal expansion coefficient [TEC]: 8.5 µm/m*K); 48 restorations (Ceram-S group) were veneered with a commercially available low-fusing ceramic optimized for zirconia frameworks (TEC: 9.5 µm/m*K). All restorations were luted with zinc-phosphate cement. Statistical analysis was performed according to the Kaplan-Meier method; time-dependent success rates of the different types of ceramic veneers were analyzed using the log-rank test. Results: Seven restorations were lost: 4 due to technical complications and 3 due to biologic complications. The overall survival rate after 48 months was 94% (Kaplan-Meier analysis). Twenty-three events required clinical intervention for restoration maintenance: 13 ceramic veneer chippings (polishing), 6 losses of retention (recementation), 3 caries lesions (filling therapy), and 1 loss of vitality (endodontic treatment). Between the two groups of veneering materials, no significant difference in the probability for success was determined (log-rank test, P = .81). Conclusions: Within a mean observation period of 4 years, sufficient survival rates for zirconia-based posterior FPDs could be verified. The main complications included fracture of the ceramic veneering material and decementation, which occurred mainly in the mandible.