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. Fifty-one 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. Int J Prosthodont 2010;23:141–148.