The molecular details of the clinical side effects of nonsteroidal anti-inflammatory drugs are poorly understood. In order to better understand the molecular basis of these effects, the interactions of Ibuprofen, Naproxen and Diclofenac with dimyristoylphosphatidylethanolamine (DMPE) phospholipid bilayers as model for a cell membrane were performed. By applying FTIR, data for the headgroup vibrations give no indication for an essential contribution of this molecular part, in particular the phosphate bands, in the interaction with the NSAID. In contrast, the evaluation of lipid vibrational bands of DMPE indicates a considerable fluidization of its hydrocarbon chains, being strongest for Diclofenac. Summarizimg the data also from ITC and DSC experiments, it can be stated that the interaction is essentially entropy driven.