BACKGROUND: Vo_2peak has traditionally been thought to be regulated by cardiac output and arteriovenous-oxygen difference. A “muscle-centric” view suggests the cardiovascular system is secondarily responsive to the primary driver: active muscle mass.METHODS: A total of 19 recreationally active men (N = 10) and women (N = 9) performed a Vo_2peak test, a Vo_2peak verification test on an electrically braked cycle ergometer on the same day, and a hydrostatic weighing test to assess fat free mass after providing written informed consent.RESULTS: Vo_2peak was significantly higher in men (3.74 ± 0.6 L · min⁻¹) than women (2.22 ± 0.30 L · min⁻¹). Whole body fat free mass explained 91% of the variability in Vo_2peak (R² = 0.91) in the men and women combined, 81% of the variability in Vo_2peak in men alone, and 46% of the variability in Vo_2peak in women alone. None of these subjects were highly trained.DISCUSSION: Fat free mass, a surrogate for muscle mass, was the primary predictor of Vo_2peak in this group of recreationally active men and women. Therefore, it appears that whole body fat free mass (a surrogate for muscle mass) is the primary driver for Vo_2peak in these recreationally active men and women. These data have implications as to the type of training NASA personnel should be undertaking: resistance training as opposed to aerobic training.Lambert CP. Whole body fat free mass and Vo_2peak in recreationally active men and women. Aerosp Med Hum Perform. 2020; 91(2):102–105.