A system for generating a digital subtraction image of at least two input images. The system comprises a registration subsystem (1) for generating a plurality of different registrations of the input images (7, 8), based on different values of a registration parameter (6). The system further comprises a subtraction subsystem (2) for generating a plurality of subtracted images by subtracting the input images in accordance with respective ones of the plurality of registrations. The system further comprises a combining subsystem (3) for combining the plurality of subtracted images into a combined subtracted image (9). The registration parameter (6) represents an assumed depth of an object which is visible in the input images (7, 8). The combining subsystem (3) is arranged for assigning a combined pixel value to a pixel position of the combined subtracted image, based on pixel values of or around corresponding pixel positions in the plurality of subtracted images.