The friction behaviour of five medical compression stockings (MCSs) against forearm skin was investigated in vivo as a function of normal load under dry and wet conditions. In addition, the interfacial moisture transport and skin hydration were analysed to understand the influence on friction. The friction coefficients of dry fabrics showed no significant differences between a traditional MCS and versions with modified material composition and base structure. Under wet conditions, the modified MCS fabrics showed considerably lower friction coefficients than the traditional MCS fabric. Changes in the material composition led to 20–30 % lower friction coefficients, different base structures to 50–60 % lower friction. The water transport properties of the MCS fabrics suggest that removal of interfacial water is useful for reducing the friction between MCSs and skin. The results provide information for the optimisation of MCSs regarding improved comfort and moisture transport properties.