All astronauts experience some degree of orthostatic intolerance following spaceflight, ranging from tachycardia to orthostatic hypotension and syncope. The purpose of this study was to evaluate the ability of two compression garments, the National Aeronautics and Space Administration's inflatable antigravity suit (AGS) and the Russian Federal Space Agency's non-inflatable compression garment (Kentavr), to prevent hypovolemia-related orthostatic intolerance.To mimic the plasma volume loss experienced by astronauts during spaceflight 19 healthy subjects received an intravenous dose of a diuretic, furosemide (0.5 mg x kg(-1)), and then consumed a low-salt diet for 36 h. Thereafter, subjects participated in a 15-min 80 degrees head-up tilt test wearing either the AGS (N = 9) or Kentavr (N = 10). Compression garments were used in the fashion recommended by the respective agencies, delivering approximately 78 mmHg and approximately 30 mmHg of compression in the AGS and Kentavr, respectively. Incidence of presyncope and hemodynamic responses during upright tilt were compared to a separate group of hypovolemic control subjects (N = 16).Subjects wearing the AGS or Kentavr completed the full 15 min of upright tilt without incidence of orthostatic hypotension or presyncope. In contrast, only 9 control subjects (56%) were able to complete the tilt test. In addition, both types of compression garments maintained systolic blood pressure and significantly reduced tilt-induced tachycardia and reductions in stroke volume.Although both garments successfully countered hypovolemia-induced orthostatic intolerance, the Kentavr provided protection by using lower levels of compression. Determining the optimal compression level required for protection of intolerance may improve crewmember comfort and decrease restrictions on physical activities after spaceflight.