Supplemental Digital Content is available in the text. Rotating impeller actuated by electromagnet has been a key technological innovation which surpassed earlier limitations of pulsatile pumps. Current impeller design, however, is alien to the functional unit of the human circulatory system and remains a potential cause of adverse prothrombotic events such as hemolysis or pump thrombosis by forcing blood cells to pass over a narrow space available within the rapidly alternating blades attached along its central hub, creating fundamentally a nonphysiologic flow, especially for miniaturized percutaneous blood pumps. Here, we present a biologically inspired, open, helicoid (BiO-H) impeller design for a circulatory assist device that has a fundamentally different footprint from the conventional Archimedean screw-based impeller designs by implementing new design features inspired by an avian right atrioventricular valve. Design parameters including an inner diameter, helix height, overall height, helix revolutions/pitch, blade length, blade thickness, introductory blade angle, number of blades, and blade shape were optimized for maximum output volumetric flow rate through the parametric analysis in computational fluid dynamics simulation. BiO-H shows an improved flow path with 2.25-fold less cross-sectional area loss than the conventional impeller designs. BiO-H with a diameter of 15 mm resulted in a maximum flow rate of 25 L/min at 15,000 revolutions per minute in simulation and showed further improved pressure–flow relationship in benchtop experiments. The design shows promise in increasing flow and could serve as a new impeller design for future blood pumps.