Purpose: Calf venous compliance ( C) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure ( P) transmission and the impact of net fluid filtration ( F) on C. The aim was to validate VOP in the lower limb and to develop a model to correct for F during VOP. Methods: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s. Intravenous pressure ( P) was measured simultaneously. C was determined with the commonly used equation [Compliance = β + 2 β × P] describing the pressure-compliance relationship. A model was developed to identify and correct for F. Results: Transmission of P to P was 100 %. The decrease in P correlated well with P reduction ( r = 0.99, P < 0.001). Overall, our model showed that C was underestimated when F was not accounted for (all P < 0.01). F was higher in women ( P < 0.01) and showed a more pronounced effect on C compared to men ( P < 0.05). The impact of F was similar during 4- and 8-min VOP. Conclusions: P is an adequate substitute for P in the lower limb. F is associated with an underestimation of C and differences in the effect of F during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function.