Under optimized synthesis conditions we prepared, for the first time, polyisobutylene-based polyurethane (PIB-PU) with 70% PIB soft segment (i.e., a bioinert and calcification resistant PU) with Mn >100,000 Da, 32 MPa ultimate strength and 630 % elongation. The key parameters for this achievement were (a) the precise stoichiometry of the polyurethane forming reaction, specifically the use of highly purified diisocyanate (MDI), and (b) the increased the solid content of the synthesis solution to the limit beyond which increased viscosity prevents stirring. The shape of the stress-strain trace of PIB-PU indicates two-step failure starting with a reversible elastic (Hookean) region up to ~50 % yield, followed by a slower linearly increasing high modulus deformation region suggesting the strengthening of PIB soft segments by entanglement/catenation, and the hard segments by progressively ordering urethane domains. This PIB-PUs is a candidate for a fully synthetic bioprosthetic heart valve since preliminary studies show that PIB-PU has impressive fatigue life.