Objective: To determine whether the oxygen uptake (VO 2 ) during walking at different speeds in people with multiple sclerosis is underestimated by available prediction equations and whether such underestimation relates to the validity of their assumptions. Design: Cross-sectional comparison. Subjects: Eighteen adults with multiple sclerosis and 18 adults without multiple sclerosis. Methods: VO 2 was measured at rest and during treadmill walking at 2.0, 3.0 and 4.0 mph with open-circuit

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... ry. The actual VO 2 was compared with that estimated by both the American College of Sports Medicine and the van der Walt and Wyndham equations. Results: The differences between the actual VO 2 and that estimated by both equations were significantly higher than zero across speeds for both groups (p < 0.001). The underestimation increased with increasing speed (p < 0.001) for both groups and was greater for participants with multiple sclerosis than those without multiple sclerosis (p < 0.011). The inaccurate prediction by the American College of Sports Medicine formula was associated with an underestimation of the net VO 2 per meter (p < 0.001), and this was higher for participants with multiple sclerosis (p < 0.007). Conclusion: Rehabilitation and exercise professionals should recognize that the American College of Sports Medicine and the van der Walt and Wyndham equations underestimate VO 2 during treadmill walking in individuals with and without multiple sclerosis.