INTRODUCTION: With increasing engagement of commercial spaceflight participants in spaceflight activities, the evaluation of individuals with medical conditions not previously characterized in the spaceflight environment is of particular interest. Factors such as acceleration forces experienced during launch, reentry, and landing of spacecraft could pose an altered risk profile in some individuals due to known disease. Bleeding diatheses present a unique concern in the spaceflight environment given hypergravity exposure and, particularly, the potential for injury resulting from transient or impact acceleration. CASE REPORT: A 26-yr-old Caucasian man with severe hemophilia A and no detectable endogenous Factor VIII (FVIII) volunteered for participation in hypergravity exposures simulating spaceflight. His treatment regimen included 50 IU · kg -1 FVIII-Fc fusion protein intravenous administration every 96 h, with supplemental FVIII administration as needed for injury or bleeding. The subject experienced two profiles at the National Aerospace Training and Research Center (NASTAR), with maximum exposure +4.0 G z , +4.5 G x , 6.1 G resultant, and maximum onset rate <0.5 G z · s -1 and +1 G x · s -1 . The subject reported no abnormal events during the profiles other than brief mild vertigo. No petechial hemorrhage, ecchymosis, or other bleeding was noted during or after profiles. Supplemental FVIII was not required before, during, or after exposure. DISCUSSION: Inherited bleeding disorders present several potential concerns that must be evaluated prior to spaceflight participation. Cautious review and management of medical history, adherence and barriers to treatment, duration of spaceflight and longitudinal management concerns, and a thorough and detailed risk/benefit assessment may provide a future pathway for inclusion of individuals with hematological disorders in commercial spaceflight. Reeves IA, Blue RS, Auñon-Chancellor S, Harrison MF, Shah R, Powers WE. Tolerance of centrifuge-simulated commercial spaceflight in a subject with hemophilia A . Aerosp Med Hum Perform. 2023; 94(6):470-474.