Background The cardiovascular system is strongly dependent on the gravitational environment. Gravitational changes cause mechanical fluid shifts and, in turn, autonomic effectors influence systemic circulation and cardiac control. We implemented a tilt paradigm to (1) investigate the acute hemodynamic response across a range of directions of the gravitational vector, and (2) to generate specific dose‐response relationships of this gravitational dependency. Methods and Results Twelve male subjects were tilted from 45° head‐up tilt to 45° head‐down tilt in 15° increments, in both supine and prone postures. We measured the steady‐state hemodynamic response in a range of variables including heart rate, stroke volume, cardiac output, oxygen consumption, total peripheral resistance, blood pressure, and autonomic indices derived from heart rate variability analysis. There is a strong gravitational dependence in almost all variables considered, with the exception of oxygen consumption, whereas systolic blood pressure remained controlled to within ≈3% across the tilt range. Hemodynamic responses are primarily driven by differential loading on the baroreflex receptors, combined with differences in venous return to the heart. Thorax compression in the prone position leads to reduced venous return and increased sympathetic nervous activity, raising heart rate, and systemic vascular resistance while lowering cardiac output and stroke volume. Conclusions Gravitational dose‐response curves generated from these data provide a comprehensive baseline from which to assess the efficacy of potential spaceflight countermeasures. Results also assist clinical management of terrestrial surgery in prone posture or head‐down tilt positions.