The ability of three novel polymers to protect phosphatidylethanolamine/phosphatidylserine (1:1) vesicles against calcium-induced destabilization (dye leakage) has been investigated. The polymers are a telechelic, hydrophobically terminated poly(ethylene glycol) (PEG), a polymer of the macromonomer PEG(8000)-lysine-stearylamide, and a hydrophobically modified poly(acrylic acid). These polymers are predominantly hydrophilic but have multiple hydrophobic moieties which serve to anchor them in the lipid bilayers. Like singly anchored PEG, the two PEG-based polymers were able to provide effective stabilization at concentrations sufficient to produce a polymer ''brush'' on the liposome surface. Interestingly, the poly(acrylic acid) polymer did not provide full stabilization even at concentrations that should have produced brush coverage, possibly owing to a more expanded polymer conformation. The potential advantages of stabilization with polymers having multiple "sticky feet'' are discussed.