Conventional mock circulatory loops (MCLs) cannot replicate realistic hemodynamic conditions without inducing blood trauma. This constrains in-vitro hemocompatibility examinations of blood pumps to static operating conditions that do not reflect clinical scenarios. This study aimed at developing an atraumatic MCL based on a hardware-in-the-loop concept (H-MCL) that enables hemocompatibility assessment under realistic hemodynamic conditions. The atraumatic H-MCL was designed for 450±50 ml of blood with the sole blood-contacting components being the polycarbonate reservoirs, the silicone/polyvinyl-chloride tubing and the blood pump under investigation. To account for inherent coupling effects a decoupling pressure control was derived by feedback linearization, whereas the level control was addressed by an optimization task to overcome periodic loss of controllability. The HeartMate 3 was showcased to evaluate the H-MCL’s accuracy at typical hemodynamic conditions and to demonstrate the H-MCL’s atraumatic properties. Pilot hemolysis experiments were conducted with bovine (n=2) and human (n=2) blood, and evaluated in terms of the normalized index of hemolysis (NIH). Typical hemodynamic scenarios of patients with full and partial support were replicated with marginal coupling effects and root mean square error (RMSE) of 1.74±1.37 mmHg and 0.94±0.83 mmHg, respectively, while the fluid level did not exceed a range of ±4% of its target value. The initial examinations of hemolysis demonstrated the atraumatic characteristics of the novel H-MCL, as evidenced by levels of NIH (bovine: 5.1-7.2mg/100L; human: 1.6-1.8mg/100L) that are consistent with those reported in existing literature. Collectively, these findings indicated the H-MCL’s potential for in-vitro hemocompatibiltiy assessment of blood pumps within realistic hemodynamic conditions.