Elastic　compression　stockings　(ECSs)　are　essential　for　the　prevention　and　treatment　of　venous　disorders　of　the　lower　limbs.　Finite　element　modeling　(FEM)　is　an　effective　method　for　numerically　analyzing　ECS　pressure　performance　for　guiding　ECS　material　design　and　pressure　dose　selection　in　treatment.　However,　existing　FEM　studies　have　primarily　used　the　two-dimensional　(2D)　mechanical　properties　(i.e.,　properties　along　the　wale　and　course　directions)　of　ECS　fabrics　and　ignored　their　three-dimensional　(3D)　mechanical　properties　(i.e.,　those　along　the　thickness　direction),　causing　deviations　in　pressure　predictions.　To　address　this　limitation,　the　present　study　developed　a　new　approach　for　determining　the　3D　mechanical　properties　of　ECS　fabrics　through　orthotropic　theoretical　analysis,　analytical　model　development,　FEM,　and　experimental　testing　and　validation.　The　results　revealed　that　the　deviation　ratios　between　the　experimental　and　simulated　pressure　values　of　ECS　fabrics　was　19.3%　obtained　using　the　2D　material　mechanical　properties　that　was　reduced　to　10.3%　obtained　using　the　3D　material　mechanical　properties.　Equivalently,　the　FEM　simulation　precision　increased　by　46.6%.　These　results　indicate　that　the　proposed　approach　can　improve　finite　element　analysis　efficiency　for　ECS　pressure　prediction,　thus　facilitating　the　functional　design　of　elastic　compression　materials　for　improving　compression　therapeutic　efficacy.　©　2022　The　Authors