Electrospun nanofibrous mats represent a new generation of medical textiles with promising applications in heart valve tissue reconstruction. It is important for biomaterials to mimic the biological and mechanical microenvironment of native extracellular matrix (ECM). However, the major challenges are still remaining for current biomedical materials, including appropriate mechanical properties, biocompatibility, and hemocompatibility. In the present work, the novel composite nanofibrous mats of poly(p-dioxanone) (PDO) and poly(ester-urethane)ureas (PEUU) are fabricated by electrospinning system. The optimal combination ratio of PDO to PEUU may balance the mechanical properties and cellular compatibility to match the newly formed tissue. In PDO/PEUU composite nanofibrous mats, PEUU can provide the biomimetic elastomeric behavior, and PDO could endow the excellent biocompatibility. In comparison to nanofibrous mat of neat PDO, the composite showed significantly improved mechanical properties, with 5-fold higher initial elongation at break. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured on the composite to evaluate its ability to rapidly endothelialize as heart valve tissue engineering. The results revealed that PDO/PEUU composite nanofibrous mats could promote cell adhesion and proliferation, especially for the ratio of 60/40. Overall, PDO/PEUU composite nanofibrous mats (60/40) show the excellent mechanical properties, appropriate biocompatibility and hemocompatibility which meet the necessary norm for tissue engineering and may be suitable for potential heart valve tissue reconstruction.