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Venous thrombosis (VT) volume assessment, by verifying its risk of progression when anticoagulant or thrombolytic therapies are prescribed, is often necessary to screen life-threatening complications. Commonly, VT volume estimation is done by manual delineation of few contours in the ultrasound (US) image sequence, assuming that the VT has a regular shape and constant radius, thus producing significant errors. This paper presents and evaluates a comprehensive functional approach based on the combination of robust anisotropic diffusion and deformable contours to calculate VT volume in a more accurate manner when applied to freehand 2-D US image sequences. Robust anisotropic filtering reduces image speckle noise without generating incoherent edge discontinuities. Prior knowledge of the VT shape allows initializing the deformable contour, which is then guided by the noise-filtering outcome. Segmented contours are subsequently used to calculate VT volume. The proposed approach is integrated into a system prototype compatible with existing clinical US machines that additionally tracks the acquired images 3-D position and provides a dense Delaunay triangulation required for volume calculation. A predefined robust anisotropic diffusion and deformable contour parameter set enhances the system usability. Experimental results pertinence is assessed by comparison with manual and tetrahedron-based volume computations, using images acquired by two medical experts of eight plastic phantoms and eight in vitro VTs, whose independently measured volume is the reference ground truth. Results show a mean difference between 16 and 35 mm3 for volumes that vary from 655 to 2826 mm3. Two in vivo VT volumes are also calculated to illustrate how this approach could be applied in clinical conditions when the real value is unknown. Comparative results for the two experts differ from 1.2% to 10.08% of the smallest estimated value when the image acquisition cadences are sim- ilar.