In image-guided therapy, high-quality preoperative images serve for planning and simulation, and intraoperatively as "background", onto which models of surgical instruments or radiation beams are projected. The link between a preoperative image and intraoperative physical space of the patient is established by image-to-patient registration. In this paper, we present a novel 3-D/2-D registration method. First, a 3-D image is reconstructed from a few 2-D X-ray images and next, the preoperative 3-D image is brought into the best possible spatial correspondence with the reconstructed image by optimizing a similarity measure (SM). Because the quality of the reconstructed image is generally low, we introduce a novel SM, which is able to cope with low image quality as well as with different imaging modalities. The novel 3-D/2-D registration method has been evaluated and compared to the gradient-based method (GBM) using standardized evaluation methodology and publicly available 3-D computed tomography (CT), 3-D rotational X-ray (3DRX), and magnetic resonance (MR) and 2-D X-ray images of two spine phantoms, for which gold standard registrations were known. For each of the 3DRX, CT, or MR images and each set of X-ray images, 1600 registrations were performed from starting positions, defined as the mean target registration error (mTRE), randomly generated and uniformly distributed in the interval of 0-20 mm around the gold standard. The capture range was defined as the distance from gold standard for which the final TRE was less than 2 mm in at least 95% of all cases. In terms of success rate, as the function of initial misalignment and capture range the proposed method outperformed the GBM. TREs of the novel method and the GBM were approximately the same. For the registration of 3DRX and CT images to X-ray images as few as 2-3 X-ray views were sufficient to obtain approximately 0.4 mm TREs, 7-9 mm capture range, and 80%-90% of successful registrations. To obtain similar results for MR to X-ray registrations, an image, reconstructed from at least 11 X-ray images was required. Reconstructions from more than 11 images had no effect on the registration results.