A method and apparatus for setting registration in a multicolor printing machine for the digital production of color separations, the actions of setting up and combining color separations being controlled when printing substrates of a different grade are fed in, in order to correct registration setting. In the event of a change in the printing substrate grade, the influence of this change on registration can be compensated for optimally before the printing substrate (16) is fed to the printing process. When the printing substrate grade is changed, the influence of all the properties of the printing substrate (16) that are relevant to registration is taken into account directly as the change is implemented, by correction values (4, 4′, . . . ) for the printing substrate (16) that are available before printing is carried out.