Over the years, several polymers have been developed for use in prosthetic heart valves as alternatives to xenografts. However, most of these materials are beset with a variety of issues, including low material strength, biodegradation, high dynamic creep, calcification, and poor hemocompatibility. We studied the mechanical, surface, and flow-mediated thrombogenic response of poly(Styrene-coblock-4-vinylbenzocyclobutene)-polyIsoButylene-poly(Styrene-coblock-4-vinylbenzocylcobutene) (xSIBS), a thermoset version of the thermoplastic elastomeric polyolefin poly(Styrene-block-IsoButylene-block-Styrene) (SIBS), which has been shown to be resistant to in vivo hydrolysis, oxidation, and enzymolysis. Uniaxial tensile testing yielded an ultimate tensile strength of 35 MPa, 24.5 times greater than for SIBS. Surface analysis yielded a mean contact angle of 82.05° and surface roughness of 144 nm, which was greater than for poly(Δ-caprolactone) (PCL) and poly(methyl methacrylate) (PMMA). However, the change in platelet activation state, a predictor of thrombogenicity, was not significantly different from PCL and PMMA after fluid exposure to 1 dyne/cm2 and 20 dyne/cm2. In addition, the number of adherent platelets after 10 dyne/cm2 flow exposure was on the same order of magnitude as PCL and PMMA. The mechanical strength and low thrombogenicity of xSIBS therefore suggest it as a viable polymeric substrate for fabrication of prosthetic heart valves, and other cardiovascular devices.