Purpose: To systematically evaluate and compare the clinical performance of translucent zirconium dioxide 3-, 4- and 5-unit fixed dental prosthesis (FDPs) in the posterior dentition, designed either monolithic or with veneered buccal cutbacks (semi-monolithic). Materials and methods: Thirty-one patients treated by general practitioners received in all thirty-one translucent zirconium dioxide FDPs, randomized to be either monolithic or semi-monolithic with a porcelain-veneered buccal cutback. Choice of design was blinded. Clinical evaluations were made using the California Dental Association (CDA) criteria and a questionnaire was used to include patient-reported outcomes and to compare them with rating from the dentists. Results: Mean follow-up time was 48.7 months (SD = 7.7). No FDP fractured during the observation period and no chip-off fractures could be detected. The overall success rate was 85.2% One monolithic FDP was found with caries and one semi-monolithic FDP was endodontically treated, giving an overall survival rate of 92.6%. Two FDPs, both semi- monolithic failed due to loss of retention and caries. Both patients and dentists rated the FDPs favourably regarding the aesthetic outcome and function, but the patients scored them higher than the dentists in this respect. Conclusion: Within the limitations of the study, both monolithic and semi-monolithic yttria-stabilized zirconium dioxide FDPs seems to be a reliable choice of treatment for 3- to 5-unit restorations in the posterior dentitions. The aesthetic advantages with porcelain veneer compared to monolithic design, might however be of less importance in the posterior regions for most patients.