The synthesis, characterization, and structure-property behavior of polyurethanes containing polyisobutylene (PIB)/poly(tetramethylene oxide) (PTMO) soft co-segments and bis(4-isocyanatocyclohexyl)methane (HMDI)/hexanediol (HDO) hard segments is presented. The mechanical (stress/strain, hardness, and hysteresis) properties of these novel polyurethanes were investigated over a broad composition range. PIB-based polyurethanes with HMDI/HDO hard segments showed better mechanical properties than earlier polyurethanes containing highly crystalline hard segments. The addition of moderate amounts (20% by weight) of PTMO significantly increased both tensile strengths and elongation. In the presence of larger amounts of PIB, these polyurethanes are expected to possess oxidative/hydrolytic/enzymatic stabilities superior to commercially available polyurethanes. These polyurethanes are softer and exhibit hysteresis superior to or comparable with conventional polyurethanes. According to initial thermal studies, these materials show good melt processibility. Overall, the mechanical properties of PIB based hybrid polyurethanes are similar to commercially important polyurethane type biomaterials. Our results show that the incorporation of PTMO segments to PIB-based polyurethanes significantly improves elastomeric properties. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5278-5290, 2009