As a widely accepted prophylaxis for deep vein thrombosis, the underlying mechanism of compression stocking still remains unclear. In this study, computational fluid dynamics was applied to in vivo data to provide quantitative insight into the hemodynamic response of the deep venous system to static external compression. The geometry and flow information of deep veins before and after compression was acquired from ten healthy volunteers using magnetic resonance imaging. Our results indicated that application of the compression stocking led to a small reduction in blood flow rate but a significant reduction in cross-sectional area of the peroneal veins in the calf, resulting in an increase in wall shear stress (WSS), but the individual effects were highly variable. The mean volume reduction of the deep veins was 58%, while the time-averaged WSS showed an average increase of 398% after compression (median 98%). The analysis also showed a strong linear correlation between the time-averaged WSS and mean blood velocity, suggesting that flow in the deep veins under the level of compression examined here can be approximated by Poiseuille's law despite local geometric variations. It is hoped that quantitative analysis of WSS in the deep venous system will aid in the future design and optimisation of the compression stocking.