Fatigue may limit the ability of people with multiple sclerosis (MS) to participate in walking exercises, which could ultimately reduce their benefit from physical therapy. An exercise program that minimizes the fatigue experienced by people with MS during exercise may lead to an increase in the amount of exercise being performed. The purpose of this study was to determine whether subjective feelings of fatigue differ in people with MS depending on whether they exercised intermittently or continuously. Using a within-subjects, counterbalanced crossover design, a sample of 30 individuals with MS performed 6 minutes of continuous and 6 minutes of intermittent walking 1 week apart. Fatigue was measured on the Visual Analogue Scale of Fatigue (VASF) and recorded before and after the walking conditions. A 2 × 2 repeated-measures analysis of variance was used to assess the potential effects of intermittent versus continuous walking on self-reported fatigue. A significant interaction revealed that pre-post mean self-ratings of fatigue on the VASF increased less in the intermittent condition (from 37.93 mm to 44.83 mm; difference = 6.90 mm) compared with the continuous condition (from 34.33 mm to 54.43 mm: difference = 20.10 mm) (P < .001), suggesting that patients experienced less fatigue in the intermittent condition despite walking an equivalent total duration. The interaction effect was not influenced by age, gender, disease severity or duration, use of antispasticity medication, use of assistive devices, or mood. The results suggest that people with MS may be more tolerant of, and able to perform, greater amounts of exercise if they exercise intermittently.