This study evaluated the effect of different parameters on the marginal precision of CAD/CAM-fabricated zirconia copings. Specimens(n=60) were fabricated with two different scanners and two milling systems. The copings were evaluated with respect to their mean and average maximum marginal gaps. A two-way analysis of variance (ANOVA) (α=0.05) was used to evaluate the effect of different parameters (scanner, milling process) on marginal accuracy. The mean (averaged maximum) marginal gaps ranged from 57.9 (112.2μm) to 71.0 (144.6 μm) in the “as machined" state. After manual adaptation, the respective values ranged from 54.6 (98.0 μm) to 59.9(107.7 μm). The system and manual adaptation variables were found both to have multiple significant effects on the marginal gap size and to have a complex interaction. Thus, synchronized/validated processing chains should be preferentially used to guarantee optimal fitting accuracy for CAD/CAM zirconia restorations.