BACKGROUND: Chronic ankle instability alters spinal level sensorimotor function and is hypothesized to alter supraspinal motor control mechanisms. Gait initiation is a functional task modulated by supraspinal pathways, but the effect of chronic ankle instability, a peripheral musculoskeletal impairment, on gait initiation and thus supraspinal motor control mechanisms remains unknown. PURPOSE: This study was conducted to determine if supraspinal aspects of motor control are altered in subjects with chronic ankle instability. STUDY DESIGN: Controlled laboratory study. METHODS: Subjects with chronic ankle instability (5 males, 15 females; age, 20.5 +/- 1.0 years; height, 169.8 +/- 9.8 cm; weight, 74.2 +/- 20.2 kg) and uninjured controls (4 males, 16 females; age, 20.85 +/- 1.6 years; height, 164.3 +/- 7.9 cm; weight, 64.2 +/- 10.62 kg) completed 5 gait initiation trials for each leg at a self-selected pace. The resulting trajectory of the center of pressure trace was investigated and peak center of pressure excursions in the anteroposterior and mediolateral directions, peak resultant center of pressure excursions, and average direction-specific velocities were calculated. RESULTS: Significant group x limb interactions were noted during the first (resultant center of pressure displacement [F(1,37) = 4.60, P = .04]) and second (mediolateral center of pressure displacement [F(1,37) = 3.82, P = .05]) period of gait initiation. Center of pressure displacement was reduced (impaired) in the involved limb of the chronic ankle instability group (resultant, 0.29 +/- 0.02; mediolateral, 0.72 +/- 0.02) relative to the uninvolved limb of the chronic ankle instability group (resultant, 0.32 +/- 0.02; mediolateral, 0.76 +/- 0.02) and both limbs of the control group (resultant, 0.32 +/- 0.02; mediolateral, 0.74 +/- 0.02) when the involved limb of the chronic ankle instability group served as the initial stance limb. CONCLUSION: These interactions suggest that supraspinal motor control mechanisms are altered in subjects with chronic ankle instability to place a greater emphasis on reducing the postural demands on the involved limb. CLINICAL RELEVANCE: These changes suggest that supraspinal adaptations to motor control may be an important contributor to the underlying neurophysiologic mechanism of chronic ankle instability. The presence of supraspinal adaptations in subjects with chronic ankle instability also indicates that health care providers and rehabilitation specialists treat chronic ankle instability as a global/central and not just a local/peripheral injury.