The cross-linking of supramolecular assemblies of hydrated amphiphiles is an effective method to stabilize the assembly. A well-known strategy for cross-linking of lipids in lyotropic phases is the inclusion of identical reactive groups in each hydrophobic tail of the lipids. An alternative approach is to incorporate two similar but distinct groups into different locations within a single hydrophobic tail of the amphiphile. In principle, these heterobifunctional amphiphiles could react to form ladderlike polymers or cross-linked polymers. This report describes the synthesis, characterization, and polymerization in lipid vesicles of two series of heterobifunctional phosphatidylcholine (PC) lipids with different separation distances between the two reactive groups. One of the groups, i.e., dienoyl (Den), is attached to the secondary oxygen of the glycerol backbone of the lipid, and the other is either an acryloyl (Acryl) or sorbyl (Sorb) functional group located at the sn-2 chain terminus. Polymerization of both reactive groups in the Acryl/DenPC or the Sorb/DenPC was achieved by either redox polymerization or direct photoirradiation. The degree of polymerization depends on the initiation chemistry. Photoirradiation yields oligomers that are insufficient to cross-link the vesicles, whereas redox-initiated radical polymerization affords cross-linked polymeric vesicles. Under radical polymerization conditions a spacer length of seven or more atoms between the two reactive groups was long enough to ensure that each reactive group can follow an independent reaction path.