Background: The “muscle hypothesis” suggests that skeletal muscle dysfunction results in abnormal muscle afferent activation leading to excessive ventilatory drive. Objective: The aim of the present study was to determine if leg muscle function is associated with ventilatory efficiency during exercise in healthy older adults since loss of skeletal muscle mass and strength is a characteristic of normal aging. Methods: Twenty-four women and 18 men aged 60-80 years performed maximal treadmill exercise for calculation of ventilatory efficiency using the ratio of ventilation to carbon dioxide at the anaerobic threshold (VE/VCO2@AT). On a separate day, participants performed leg strength testing and single-leg knee extension exercise. Results: The VE/VCO2@AT was higher in women than men (33 ± 3 vs. 30 ± 3; p=0.03). After adjustment for age and cardiorespiratory fitness, leg muscle strength (absolute quadriceps isometric force) was inversely associated with VE/VCO2@AT in women (r=-0.44, p=0.