The structure-property relationship of L-tyrosine-based polyurethanes was demonstrated by using different polyols and diisocyanates. L-tyrosine-based chain extender, desaminotyrosyl tyrosine hexyl ester (DTH), was used, to synthesize a series of polyurethanes. Polyethylene glycol (PEG) or poly caprolactone diol (PCL) was used as the soft segment and hexamethylene diisocyanate (HDI) or dicyclohexylmethane 4,4'-diisocyanate (HMDI) was used with DTH as the hard segment. The polyurethanes were characterized to investigate the effect of structure on different polyurethane properties. From FTIR and DSC, these polyurethanes exhibit a wide range of morphology from phase-mixed to phase-separated structure. The decreasing molecular weight of the PEG soft segment leads to relatively more phase mixed morphology whereas for PCL-based polyurethanes the extent of phase mixing is less with decreasing PCL molecular weight. Results show that PCL-based polyurethanes are mechanically stronger than PEG-based polyurethanes but PCL-based polyurethanes degrade slower and absorb less water compared with PEG-based polyurethanes. The HMDI-based polyurethanes are less crystalline and comparatively more hydrophobic than HDI-based polyurethartes. The characterization results show that the polyurethane properties are directly related to the structure and can be varied easily for a different set of properties that are pertinent for biomaterial applications. (C) 2008 Wiley Periodicals, Inc.