We studied the incorporation of the hydrophobic anticancer drug paclitaxel (PXL), into a variety of lipid matrices by X-ray diffraction (XRD) measurements. Liposome suspensions from cationic and zwitterionic lipids, containing different molar fractions of paclitaxel were made and deposited on planar glass substrates. After drying at controlled relative humidity, aligned multilayer stacks were obtained. The structure perpendicular to the substrate plane was investigated by X-ray diffraction measurements. Bragg peaks to several orders were detected, indicative of well-ordered multilamellar lipid layers. The drug induced a modification of the bilayer spacing, which was the characteristic for a given type of lipid matrix. With an excess of the drug, Bragg peaks of drug crystals could be observed. The results provide insight into the solubility of paclitaxel in the different lipid membranes. A structural model of the organization of the drug in the membrane was discussed.