Platelet adhesion and activation are key events in thrombus or clot formation on blood-contacting biomaterials. Thus understanding the complex interactions between biomaterial surface properties and platelets is important for developing vascular access devices that limit thromboembolic events. Medical-grade poly(urethanes) are frequently used in blood-contacting medical devices due to their desirable mechanical properties and high level of hemocompatibility. Moreover, it has been shown that sub-platelet-sized micropatterns reduce platelet adhesion. Based on this evidence, we hypothesized that bio-inspired, antifouling Sharklet™ (SK) microtopographies replicated in biomedical thermoplastic poly(urethane) (TPU) reduce both platelet adhesion and activation compared to smooth (SM) controls.