The development of drug delivery systems, sensors and other devices based on liposomes (small unilamellar lipid vesicles, SUVs) requires the adsorption of intact lipid structures onto solid surfaces in the first place. In this work, we report on the in situ investigation of the adsorption of liposomes of 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DPPG) onto a rough surface by neutron reflectivity. Rough surfaces are achieved by preparing polyelectrolyte layer-by-layer films, which act as soft polymer cushions. Neutron reflectivity measurements performed at the solid/D
O interface allow for the determination of the thickness of the adsorbed structures. The conducted investigation proofs that the liposomes dispersed in the liquid phase are generally adsorbed intact onto the cushion surface, confirming that the roughness of the latter is a variable to be taken into account if one intends to adsorb intact lipid structures. Liposome flattening is observed and justified by the attractive electrostatic interactions occurring between the negatively charged lipid liposomes and the outermost, positively charged polyelectrolyte layer of the cushion. The conducted measurements further demonstrate that the adsorbed liposomes are stable for several hours. These findings are fundamental for the development of devices based on immobilized but intact SUVs on sensor surfaces.