A method for operating a multiple axis machine includes controlling drives of the machine with a machine control system and monitoring the machine with a fail-safe control system having first and second redundant channels. Each of the first and second channels receives first input target values and first input actual values from the machine control system, and compares first reference target values (based on the first input target values) with first reference actual values (based on the first input actual values). A fault reaction is triggered if there is a deviation between the compared values that exceeds a specified tolerance. The first input values comprise reference position values of a machine-fixed reference or time derivatives thereof, and the machine control system determines target and/or actual reference position values based on a transformation between reference position values of the machine-fixed reference and axial position values of the machine.