A method for operating an internal combustion engine with an exhaust gas aftertreatment device has a control system that determines a vector field of corresponding engine operating points (nEngi, MEngi) depending on a predetermined reducing agent-fuel consumption weighting qFD to be maintained during the operation of the internal combustion engine in order to derive a specific DEF-fuel consumption BSFCi for each of the engine operating points (nEngi, MEngi). The control system selects the element iSet from the identified vector field to which a minimum specific DEF-fuel consumption BSFCSet corresponds as the setpoint engine operating point (nEngSet, MEngSet), wherein the control system specifies a setpoint engine speed nEngSet according to the selected element iSet and specifies therefrom a setpoint gear ratio rSet, taking into account a current gearbox output speed nout.