We synthesized and characterized novel amphiphilic invertible polyurethanes (AIPUs) that had both hydrophilic (poly(ethylene glycol), PEG) and hydrophobic (polytetrahydrofuran, PTHF) constituents. Two different synthetic approaches produced macromolecules with random and alternating distributions of hydrophilic and hydrophobic fragments along the main backbone. Alternating AIPUs are soluble in both polar and nonpolar organic solvents but are insoluble in water. The insolubility of alternating AIPUs in water can be explained by microphase separation that results in formation of hard segment domains (crystallites) and by strong intermolecular (hydrogen) bonding between urethane groups. In contrast, random AIPUs are soluble in both organic and aqueous media. The environment-dependent formation of AIPU micelles (both random and alternating), whose behavior could be correlated with their chemical structure, has been shown by viscosity measurements and confirmed by H-1 NMR spectroscopic study. We foresee that the amphiphilic properties of synthesized polymers will be clearly the basis of new architectures, both in solution and on solid surfaces, and that these polymers have potential uses in a broad range of applications