Background Discerning the mechanisms driving orthostatic symptoms in human beings remains challenging. Therefore, we developed a novel approach combining cardiac and cerebral real‐time magnetic resonance imaging, beat‐to‐beat physiological monitoring, and orthostatic stress testing through lower‐body negative pressure (LBNP). We conducted a proof‐of‐concept study in a patient with severe orthostatic hypotension. Methods and Results We included a 46‐year‐old man with pure autonomic failure. Without and during −30 mmHg LBNP , we obtained 3T real‐time magnetic resonance imaging of the cardiac short axis and quantitative flow measurements in the pulmonary trunk and middle cerebral artery. Blood pressure was 118/74 mmHg during supine rest and 58/35 mmHg with LBNP . With LBNP , left ventricular stroke volume decreased by 44.6%, absolute middle cerebral artery flow by 37.6%, and pulmonary trunk flow by 40%. Conclusions Combination of real‐time magnetic resonance imaging, LBNP , and continuous blood pressure monitoring provides a promising new approach to study orthostatic intolerance mechanisms in human beings.