Three series of new optically active poly(amide-imide-ether-urethane) (PAIEU) copolymers with different soft segments including polyethylene glycol (PEG), polypropylene glycol (PPG) or polytetramethylene glycol (PTMG) of molecular weight (MW) of 1000 were successfully synthesized. These copolymers were prepared via direct polycondensation reaction of an aromatic diacid based on L-leucine (1), 4,4'-methylene-bis-(4-phenylisocyanate) (MDI) (2) and different polyether polyols. FTIR spectroscopy shows the different absorption bands of NH, urethane and imide-I, II groups that suggests the different intermolecular interactions due to hydrogen bonding in these PAIEUs. On the other hand, DSC analysis reveals that the glass transition temperature for hard segments (Tgh) of PAIEUs based on polyethers with higher ratio of O/CH2 is higher than that of polyethers with lower ratio of O/CH2 and it decreases with the soft segment length in PAIEUs consisting of the same type of PEG soft segments.