Image-guided alignment procedures in radiotherapy aim at minimizing discrepancies between the planned and the real patient setup. For that purpose, we developed a 2D/3D approach which rigidly registers a computed tomography (CT) with two x-rays by maximizing the agreement in pixel intensity between the x-rays and the corresponding reconstructed radiographs from the CT. Moreover, the algorithm selects regions of interest (masks) in the x-rays based on 3D segmentations from the pre-planning stage. For validation, orthogonal x-ray pairs from different viewing directions of 80 pelvic cone-beam CT (CBCT) raw data sets were used. The 2D/3D results were compared to corresponding standard 3D/3D CBCT-to-CT alignments. Outcome over 8400 2D/3D experiments showed that parametric errors in root mean square were <0.18° (rotations) and <0.73 mm (translations), respectively, using rank correlation as intensity metric. This corresponds to a mean target registration error, related to the voxels of the lesser pelvis, of <2 mm in 94.1% of the cases. From the results we conclude that 2D/3D registration based on sequentially acquired orthogonal x-rays of the pelvis is a viable alternative to CBCT-based approaches if rigid alignment on bony anatomy is sufficient, no volumetric intra-interventional data set is required and the expected error range fits the individual treatment prescription.