A method for registering a 2-D DSA image to a 3-D image volume includes calculating a coarse similarity measure between a 2-D DRR of an aorta and a cardiac DSA image, and a 2-D DRR of a coronary artery and the cardiac DSA image, for a plurality of poses over a range of 2-D translations. Several DRR-pose combinations with largest similarity measures are selected as refinement candidates. The similarity measure is calculated between the refinement candidate DRRs and the DSA, for a plurality of poses over a range of 3-D translations and in-plane rotations. One or more DRR-pose combinations with largest similarity measures are selected as final candidates. The similarity measure between the final candidate DRRs the DSA are calculated for a plurality of poses over a range of 3D translations and 3D rotations, and a DRR-pose combination with a largest similarity measure is selected as a final registration result.