Many astronauts develop orthostatic intolerance following spaceflight and this change may be more prevalent in females. Although the blood pressure response to standing should normalize in the weeks following their return to Earth, there may be emergencies where an immediate short-term solution is necessary. PURPOSE: To examine the effects of different levels of blood flow restriction on blood pressure and heart rate when a person is transitioned from supine to an upright position and determine whether this change differs based on sex. METHODS: 45 men and 44 women partook in this four-visit study. The first visit included the determination of the applied pressure for the different conditions, and familiarization with the tilt table protocol. Visits 2-4 were the experimental visits completed in a randomized order on the tilt table: 1) Sham, 2) Moderate, or 3) High pressure. Brachial blood pressure was measured at baseline, upon inflation of the cuffs in a supine position, immediately after tilt (70°), and 8 more times separated by 45 seconds. RESULTS: Data are presented as mean (SD) and as a change from the baseline measurement. Changes in systolic blood pressure were pressure dependent (High > Moderate > Sham). Notably, the application of blood flow restriction was able to prevent the drop in systolic blood pressure when moving from a supine to the head-up tilt position [High vs Sham: 5.5 (7.4) mmHg, High vs Moderate: 3 (7.4), and Moderate vs Sham: 2.4 (8.4) mmHg]. Diastolic blood pressure increased following head-up tilt and changes were greatest with the High pressure with no differences between Moderate and Sham [High vs Sham: 2.4 (5.3) mmHg, High vs Moderate: 1.9 (6.3), and Moderate vs Sham: 0.6 (5.1) mmHg]. Heart rate increased following head-up tilt and the change was initially greatest in the Sham condition [High vs Sham: -3.5 (9.1) mmHg, High vs Moderate: 0.5 (9.1), and Moderate vs Sham: -3.6 (9.3) mmHg]. However, heart rate changed the most in the High pressure condition by the end of the head-up tilt period. CONCLUSIONS: The application of blood flow restriction prevented the initial drop in blood pressure when transitioning from the supine to the upright position. This could be useful when astronauts need to exit the spacecraft quickly upon landing, where a failure to maintain blood pressure could be fatal.