This paper presents a validated model of calf compression with an external pressure cuff as used for deep vein thrombosis. Magnetic resonance (MR) images of calf geometry were used to generate subject-specific finite-element (FE) models of the calf cross section. Ultrasound images of deep vessel collapse obtained through a water-filled cuff were used to validate model behavior. Calf/cuff pressure interface measurements were applied to the FE model and the resulting tissue deformation was compared with MR image in normal volunteers (three females, four males, age range 20-55) using two distinct cuffs. MR observations and the model results showed good qualitative agreement. A similar reduction in cross-sectional area of the posterior tibial veins was obtained under both symmetric compression (89%) and asymmetric compression (81%), but greater compression of the anterior tibial veins was achieved with symmetric compression. The need to account for the effective compressibility of the calf tissue suggests that external measurements of the calf tissue deformation will not accurately predict deep vessel collapse. These results have implications for the modification of venous haemodynamics by such systems and could help to improve cuff design.