INTRODUCTION: Commercial spaceflight participants (SFPs) will introduce new medical challenges to the aerospace community, with unique medical conditions never before exposed to the space environment. This is a case report regarding the response of a subject with multiple cardiac malformations, including aortic insufficiency, pulmonary atresia, pulmonary valve replacement, ventricular septal defect (post-repair), and pulmonary artery stenosis (post-dilation), to centrifuge acceleration simulating suborbital flight.CASE REPORT: A 23-yr-old man with a history of multiple congenital cardiac malformations underwent seven centrifuge runs over 2 d. Day 1 consisted of two +G_z runs (peak = +3.5 G_z, run 2) and two +G_x runs (peak = +6.0 G_x, run 4). Day 2 consisted of three runs approximating suborbital spaceflight profiles (combined +G_x and +G_z). Data collected included blood pressure, electrocardiogram, pulse oximetry, neurovestibular exams, and post-run questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. Despite the subject’s significant medical history, he tolerated the acceleration profiles well and demonstrated no significant abnormal physiological responses.DISCUSSION: Potential risks to SFPs with aortic insufficiency, artificial heart valves, or valvular insufficiency include lower +G_z tolerance, earlier symptom onset, and ineffective mitigation strategies such as anti-G straining maneuvers. There are no prior studies of prolonged accelerations approximating spaceflight in such individuals. This case demonstrates tolerance of acceleration profiles in an otherwise young and healthy individual with significant cardiac malformations, suggesting that such conditions may not necessarily preclude participation in commercial spaceflight.Blue RS, Blacher E, Castleberry TL, Vanderploeg JM. Centrifuge-simulated suborbital spaceflight in a subject with cardiac malformation. Aerosp Med Hum Perform. 2015; 86(11):999–1003.