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Low and stable friction is required for mechanical seals in implantable ventricular assist devices. In this study, a specialized test apparatus was designed to test the frictional properties of a mechanical seal in blood in implantable ventricular assist devices. It was shown that a blood-derived protein film forms on the sealing surfaces and causes higher and unstable friction than that in water. Further, it was shown that concave surface features on the substrate initially catch aggregated proteins that are denatured by friction, thus the protein film progresses from concave to flat regions on the substrate. On the basis of this protein film formation mechanism, the creation of a smooth, hydrophilic sealing surface was proposed to control friction and its effectiveness was validated.