Cone-beam CT has become commonplace for 3D guidance in interventional radiology (IR), especially for vascular procedures in which identification of small vascular structures is crucial. However, its long image acquisition time poses a limit to image quality due to soft-tissue deformable motion that hampers visibility of small vessels. Autofocus motion compensation has shown promising potential for soft-tissue deformable motion compensation, but it lacks specific target to the imaging task. This work presents an approach for deformable motion compensation targeted at imaging of vascular structures. The proposed method consists on a two-stage framework for: i) identification of contrast-enhanced blood vessels in 2D projection data and delineation of an approximate region covering the vascular target in the volume space, and, ii) a novel autofocus approach including a metric designed to promote the presence of vascular structures acting solely in the region of interest. The vesselness of the image is quantified via evaluation of the properties of the 3D image Hessian, yielding a vesselness filter that gives larger values to voxels candidate to be part of a tubular structure. A cost metric is designed to promote large vesselness values and spatial sparsity, as expected in regions of fine vascularity. A targeted autofocus method was designed by combining the presented metric with a conventional autofocus term acting outside of the region of interest. The resulting method was evaluated on simulated data including synthetic vascularity merged with real anatomical features obtained from MDCT data. Further evaluation was obtained in two clinical datasets obtained during TACE procedures with a robotic C-arm (Artis Zeego, Siemens Healthineers). The targeted vascular autofocus effectively restored the shape and contrast of the contrast-enhanced vascularity in the simulation cases, resulting in improved visibility and reduced artifacts. Segmentations performed with a single threshold value on the target vascular regions yielded a net increase of up to 42% in DICE coefficient computed against the static reference. Motion compensation in clinical datasets resulted in improved visibility of vascular structures, observed in maximum intensity projections of the contrast-enhanced liver vessel tree. Targeted motion compensation for vascular imaging showed promising performance for increased identification of small vascular structures in presence of motion. The development of autofocus metrics and methods tailored to vascular imaging opens the way for reliable compensation of deformable motion while preserving the integrity of anatomical structures in the image.