In this study we have prepared various phosphatidyl choline based colloidal systems, namely liposomes, transfersomes, microemulsions and micelles, using similar excipients and compared their ability to deliver drugs into and through the skin under occlusive and non-occlusive conditions. Hydrophilic propranolol hydrochloride (PHCl) and lipophilic propranolol base (PB) were used as model drugs. All tested parameters, that is formulation composition, drug characteristics and testing conditions, influenced skin permeability and skin retention. A trend was observed showing that the skin permeation as well as skin retention decreases with the amount of phosphatidyl choline in the formulations for both tested model drugs (micelles > transfersomes > liposomes > microemulsion). The lipophilic model drug had higher skin permeability especially when incorporated into the systems containing mainly hydrophilic excipients. Skin retention, however, was not affected by the drug hydrophilicity to the same extent as skin permeability. Occlusion increased both skin retention and skin permeation for both model drugs.