Polymer-coated liposomes, particularly poly(ethylene glycol) (PEG)-substituted liposomes, have emerged as long-circulating carrier systems for drug delivery and diagnostic purposes. A rapid synthesis of three different types of multifunctional lipids with structurally diverse hydrophilic, polyether-based architectures via one- or two-pot approaches is described. Architectural variation is achieved by the combination of different oxyanionic polymerization strategies and various glycidyl ether building units. Branched polyglycerol lipids have been prepared via cholesterol- or 1,2-bis-n-alkyl glyceryl ether-initiated, oxyanionic ring-opening polymerization (ROP) of protected glycidyl ethers and glycidol, respectively. In addition 1:0 these polyglycerol-based lipids, we describe the synthesis of multifunctional PEGs as the hydrophilic part of the lipid, which can be compared to conventional stealth lipids, but bear an adjustable number of hydroxyl functions within the PEG backbone. These lipids can be readily obtained by random copolymerization of ethylene oxide and protected glycidyl ethers, such as ethoxyethyl glycidyl ether (EEGE) and isopropylidene glyceryl glycidyl ether (IGG). Polydispersities M-w/M-n of the amphiphilic polyether structures were in the range of 1.04-1.2 for the linear structures and 1.1-1.6 for the hyperbranched lipids. Critical. micelle concentrations (CMC) have been determined via the pyrene fluorescence method and were in the range of 1.4-40.7 mg/L, correlated to molecular weight and functionality of the polar polyether segment. Liposomes containing these hydroxy-functional lipids have been prepared via the membrane extrusion method and have been visualized by transmission electron microscopy (TEM) and cryo-TEM.