Purpose <p>Compression therapy with medical graduated compression garments is commonly used in the treatment of leg lymphedema. However, the relationship between the interface pressure applied by the garment and the resulting hydrostatic pressure within the soft tissues remains poorly understood. Women commonly use thigh-high garments, whereas men often use knee-high compression garments, but the effects of these different garment types remain unclear. The objective of this study was to evaluate pressure transmission within lymphedematous legs and to assess the effects of different garment types.</p> Methods <p>Patient-specific finite element models were developed from magnetic resonance imaging data of eight female and three male lymphedematous legs. The models explicitly represented the skin, fascia cruris, subcutaneous tissue, and muscle. Interface and hydrostatic pressures were quantified for class 2 and class 3 compression garments, as well as for three garment superimposition configurations.</p> Results <p>For all legs wearing class 2 compression garments, and for female legs wearing class 3 compression garments, interface and hydrostatic pressures were below therapeutic ranges. Male legs wearing class 3 compression garments achieved hydrostatic pressure values within the therapeutic range due to higher garment stiffness. Superimposition of garments increased hydrostatic pressure in female legs and led to excessive compression in male legs.</p> Conclusion <p>These findings highlight the influence of limb morphology and garment mechanical properties on compression therapy. Class 2 or class 3 garments alone may be insufficient for female patients, whereas superimposition should be applied cautiously in male patients. Patient-specific finite element analyses may support more individualized compression therapy prescriptions.</p>