Electrospun grafts are widely investigated for vascular graft replacement due to their ease and compatibility with many natural and synthetic polymers. Here, the effect of the processing parameters on the scaffold's architecture and subsequent reactions of partially heparinized blood triggered by contacting these topographies were studied. Degrapol(®) (DP) and poly(lactic-co-glycolic acid (PLGA) electrospun fibrous scaffolds were characterized with regard to fiber diameter, pore area and scaffold roughness. The study showed that electrospinning parameters greatly affect fiber diameter together with pore dimension and overall scaffold roughness. Coagulation cascade activation, early platelet adhesion and activation were analyzed after two hours exposure of blood to the biomaterials. While no differences were found between DP and PLGA with similar topographies, the blood reactions were observed to be dependent on the fiber diameter and scaffold roughness. Scaffolds composed of thin fibers (diameter < 1μm) triggered very low coagulation and almost no platelet adhered. On the other hand, scaffold with bigger fiber diameter (2-3 μm) triggered higher thrombin formation and more platelets adhered. The highest platelet adhesion and activations rates as well as coagulation cascade activation were found in blood incubated in contact to the scaffolds produced with the biggest fiber diameter (5μm). These findings might indicate that electrospun grafts with small fiber diameter (<1μm) could perform better with a reduced early thrombogenicity by lower platelets adhesion and lower activation of platelets and coagulation cascade.