Coronary artery bypass grafting is one of the most commonly performed major surgeries in the United States. Autologous vessels such as the saphenous vein are the current gold standard for treatment; however, synthetic vascular prostheses made of expanded poly(tetrafluoroethylene) or poly(ethylene terephthalate) are used when autologous vessels are unavailable. These synthetic grafts have a high failure rate in small diameter (<4 mm) applications due to rapid reocclusion via intimal hyperplasia. Current strategies to improve clinical performance are focused on preventing intimal hyperplasia by fabricating grafts with compliance and burst pressure similar to native vessels. To this end, we have developed an electrospun vascular graft from segmented polyurethanes with tunable properties by altering material chemistry and graft microarchitecture. Relationships between polyurethane tensile properties and biomechanical properties were elucidated to select polymers with desirable properties. Graft thickness, fiber tortuosity, and fiber fusions were modulated to provide additional tools for controlling graft properties. Using a combination of these strategies, a vascular graft with compliance and burst pressure exceeding the saphenous vein autograft was fabricated (compliance=6.0 +/- 0.6%/mmHg x 10(-4), burst pressure=2260 +/- 160 mmHg). This graft is hypothesized to reduce intimal hyperplasia associated with low compliance in synthetic grafts and improve long-term clinical success. Additionally, the fundamental relationships between electrospun mesh microarchitecture and mechanical properties identified in this work can be utilized in various biomedical applications. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 313-323, 2015.