Hybrids of hydrophobic sub-2-nm-diameter dodecanethiol-coated Au nanoparticles and phosphatidylcholine (PC) lipid vesicles made by extrusion were examined by cryogenic transmission electron microscopy (cryoTEM). The nanoparticles loaded the vesicles as a dense monolayer in the hydrophobic core of the lipid bilayer, without disrupting their structure. Nanoparticle-vesicle hybrids could also be made by a dialysis process, mixing preformed vesicles with detergent-stabilized nanoparticles, but this approach led to vesicles only partially loaded with nanoparticles that segregated into hemispherical domains, forming a Janus vesicle-nanoparticle hybrid structure.