Besides load-bearing capacity, marginal accuracy is a further crucial factor influencing the clinical long-term reliability of fixed dental prostheses (FDPs). The aim of this in vitro study was to evaluate the marginal fit of four-unit zirconia bridge frameworks fabricated using four different computer-aided design (CAD)/computer-aided manufacturing (CAM) systems. Ten frameworks were manufactured using each fabricating system. Three systems (inLab, Everest, Cercon) processed white-stage zirconia blanks, which had to be sintered to final density after milling, while with one system (Digident) restorations were directly milled from a fully sintered material. After manufacturing, horizontal and vertical marginal discrepancies, as well as the absolute marginal discrepancy, were determined by means of a replica technique. The absolute marginal discrepancy, which is considered to be the most suitable parameter reflecting restorations' misfit in the marginal area, had a mean value of 58 mum for the Digident system. By contrast, mean absolute marginal discrepancies for the three other systems, processing presintered blanks, differed significantly and ranged between 183 and 206 mum. Within the limitations of this study, it could be concluded that the marginal fit of zirconia FDPs is significantly dependent on the CAD/CAM system used, with restorations processed of fully sintered zirconia showing better fitting accuracy.