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Multiple sclerosis is a neurodegenerative disease that causes balance deficits, even in early stages. Evidence suggests that people with multiple sclerosis (PwMS) rely more on vision to maintain balance, and challenging balance with optical flow perturbations may be a practical screening for balance deficits. Whether these perturbations affect standing balance in PwMS is unknown. Therefore, the purpose of this study was to examine how optical flow perturbations affect standing balance in PwMS. We hypothesized that perturbations would cause higher variability in PwMS compared with matched controls during standing and that standing balance would be more susceptible to anterior–posterior (A–P) perturbations than medial–lateral (M–L) perturbations. Thirteen PwMS and 13 controls stood under 3 conditions: unperturbed, M–L perturbation, and A–P perturbations. A–P perturbations caused significantly higher A–P trunk sway variability in PwMS than controls, although both groups had similar center-of-pressure variability. Both perturbations increased variability in A–P trunk sway and center of pressure. Trunk variability data supported the hypothesis that PwMS were more susceptible to optical flow perturbations than controls. However, the hypothesis that A–P perturbations would affect balance more than M–L perturbations was partially supported. These results suggest potential for optical flow perturbations to identify balance deficits in PwMS. [ABSTRACT FROM AUTHOR]