The aim of this in vitro study was to evaluate the marginal and internal fit of CAD/CAM-generated four-unit zirconia fixed dental prostheses made with digital and conventional impressions. A titanium master model was used. For group conventional impression (CI), 12 polyether impressions of the master model with Impregum(TM) were made. For group digital impression (DI), 12 digital impressions of the master model using Lava(TM) C.O.S. system were made. The replica technique was applied. The Mann-Whitney U statistical test was applied to detect statistical differences between the groups, in terms of marginal and internal fit. Face-by-face comparisons between groups were also carried out. Groups DI and CI presented mean marginal fit of 63.96 and 65.33 μm, respectively, and showed no statistically significant difference. Groups DI and CI presented significantly different internal fit with mean values of 58.46 and 65.94 μm, respectively. Group DI showed statistically significantly lower values for marginal and internal fit on premolar mesial face, and on molar distal and palatal faces. Frameworks fabricated from digital and conventional impressions showed clinically acceptable marginal fit. Frameworks fabricated from digital impression demonstrated better internal fit than ones fabricated from conventional impression. Reviewing each retainer face, digital impression showed better marginal and internal fit at the premolar mesial and molar distal faces. The results of this in vitro study show that digital impressions made with the Lava(TM) C.O.S. system and its digital workflow are suitable for fabricating four-unit zirconia frameworks, with regard to marginal and internal fit requirements.