A clinically approved, tissue engineered graft is needed as an alternative for small‐diameter artery replacement. Collagen type I is commonly investigated for naturally derived grafts. However, collagen promotes thrombosis, currently requiring a graft pre‐seeding step. This study investigates unique impacts of blending low collagen amounts with synthetic polymers on scaffold platelet response, which would allow for viable acellular grafts that can endothelialize in vivo. While platelet adhesion and activation are confirmed to be high with 50% collagen samples, low collagen ratios surprisingly exhibit the opposite, anti‐thrombogenic effect. Different platelet interactions in these blended materials can be related to collagen structure. Low collagen ratios show homogenous distribution of the components within individual fibers. Importantly, blended collagen scaffolds exhibit significant differences from gelatin scaffolds, including retaining percentage of collagen after incubation. These findings correlate with functional benefits including better endothelial cell spreading on collagen versus gelatin blended materials. This appears to differ from the current paradigm that processing with harsh solvents will irreversibly denature collagen into less desirable gelatin, but an important distinction is the interaction between collagen and synthetic materials during processing. Overall, excellent anti‐thrombogenic properties of low collagen blends and benefits after grafting show promise for this vascular graft strategy.