A method is provided for automatically determining a variable laterally centered setpoint for a digital radiographic imaging system that includes a radiation source and a digital detector. The variable laterally centered setpoint is determined during a setup procedure which involves providing a detector at a detector location, positioning the radiation source at a first source location, detecting a radiation field generated by the source while at the first source location, determining the lateral centerline of the detected radiation field, repositioning the source to a second source location that is laterally displaced from the first location, detecting a second radiation field, and determining the lateral centerline of the second radiation field. A lateral gain constant for the imaging system can then be determined based on the determined centerlines of the first and second radiation fields and feedback signals from position sensors that are representative of the first and second source locations. Based on the lateral gain constant and the source position feedback signal, the source can be laterally centered with respect to the lateral centerline of the detector.