We describe the spontaneous incorporation of amphiphilic gold nanoparticles (Au NPs) into the walls of surfactant vesicles. Au NPs were functionalized with mixed monolayers of hydrophilic (deprotonated mercaptoundecanoic acid, MUA) and hydrophobic (octadecanethiol, ODT) ligands, which are known to redistribute dynamically on the NP surface in response to changes in the local environment. When Au NPs are mixed with preformed surfactant vesicles, the hydrophobic ODT ligands on the NP surface interact favorably with the hydrophobic core of the bilayer structure and guide the incorporation of NPs into the vesicle walls. Unlike previous strategies based on small hydrophobic NPs, the present approach allows for the incorporation of water-soluble particles even when the size of the particles greatly exceeds the bilayer thickness. The strategy described here based on inorganic NPs functionalized with two labile ligands should in principle be applicable to other nanoparticle materials and bilayer structures.