Percutaneous mechanical circulatory support (pMCS) devices sometimes cause hemolysis. The US FDA mandates comparative in vitro testing for new devices to evaluate the risk of hemolysis. This study compared the degree of hemolysis caused by the Second Heart Assist (SHA) Whisper at its maximum pump speed with that of the Impella CP, following ASTM standards. SHA Whispers were tested at 10,000 RPM; Impella CP was operated at 44,133 ± 606 RPM to match the SHA Whisper’s flow rate in two identical in vitro blood circulatory loops using citrated bovine blood. Hemolysis was analyzed by the tetramethylbenzidine method. The change in plasma free hemoglobin (ΔpfHb) was significantly greater with the Impella CP than with the SHA Whisper (p < 0.01). Both devices caused a steady increase in pfHb, with significant differences after 60 minutes (p < 0.01). For SHA Whisper and Impella CP, there were significant difference in NIH (0.088 ± 0.022 versus 0.194 ± 0.029 g/100, P < 0.01), and MIH (9.72 ± 2.4 versus 20.83 ± 3.5, P < 0.01). Thus, the SHA Whisper was more hemocompatible than the Impella CP under the same hemodynamic conditions. These benchmark values will aid future in vitro blood testing for pMCS devices.