Although the hemocompatibility of left-ventricular assist devices (LVADs) has continuously improved, assessment of hemolysis remains mandatory in pre-clinical testing. The ASTM-F1841 has standardized this assessment since 1997. However, the recommended usage of fresh, non-pooled human blood is hardly feasible with the test loop volume specified therein, when testing the device under test versus a predicate device as required by the international standard 10993-4. In this study, we compared ASTM-conforming (ASTM) and downscaled (mini) test loops with a one-third priming volume for the assessment of blood damage at the ASTM operating point. Blood damage was assessed for HeartMate 3 and BPX-80 in 6 experiments with heparinized porcine slaughterhouse blood for 6 h. We analyzed plasma free hemoglobin (pfHb), von Willebrand factor (vWF) concentration and collagen-binding functionality and calculated indices of hemolysis and vWF-ratios. The mini test loops provided significantly higher pfHb increase and consistently stronger vWF-ratio decrease and yielded a significantly better differentiation of the pumps. Interestingly, indices of hemolysis were generally lower in the mini set-up, indicating less adverse effects by the mini loop itself. Thus, we propose our mini test loop as suitable tool for clinically relevant standardized assessment of blood damage by future LVADs with single-donation human blood.