The contact and friction behavior of a medical compression stocking (MCS) under different strains was investigated in friction and compression experiments against a mechanical skin model. In addition, the 3D topography of the MCS surfaces was analyzed in order to study the relationship between macroscopic friction and microscopic surface properties. The load dependence of friction coefficients was found to be in accordance with the adhesion friction model. The surface structure of MCS samples was considerably changed when varying the strain state, while friction coefficients remained comparable, indicating real contact areas independent of strain on the microscopic level. The experimental findings could be confirmed and explained on the basis of the microscopic surface analyses, when interpreting the fabric surfaces to be composed of numerous individual round asperities obeying the Hertz contact model.