Poly(ethylene glycol), PEG, is normally coupled to hydrophobic molecules to produce nonionic surfactants. However, there is no report so far on cationic surfactants in which PEG chain acts as a hydrophobic tail. In this work, two novel cationic amphiphiles containing a poly(ethylene glycol) monomethyl ether (mPEG) tail different lengths linked to a cationic headgroup were synthesized to investigate their surface activity and self-assembling properties. The amphiphiles were shown to be surface-active with low critical micelle concentration (cmc). It has been found that although mPEG chain is hydrophilic as compared to hydrocarbon chain of equivalent length, the cmc values are lower than that of cetyltrimethylammonium chloride, a commercial cationic surfactant. The cationic surfactants have been shown to have antimicrobial activity. The fluorescence probe studies and the thermodynamic data have shown that the self-assembly is due to strong van der Waals interaction between mPEG chains as well as hydrophobic effect. The single-tailed cationic surfactants spontaneously self-assembled to form small unilamellar vesicles with hydrodynamic diameter in the range of 20-50 nm. The vesicles were characterized by fluorescence probe technique, dynamic light scattering, transmission electron microscopy, and confocal fluorescence microscopy. We have also studied encapsulation of model drugs by the vesicles and pH-triggered release kinetics.