Objective To determine the potential to improve driving-related skills using a simulator-based program in persons with relapsing-remitting multiple sclerosis (RRMS). Design Pre-post intervention. Setting A university driving simulator laboratory. Participants Participants (N=50) with RRMS and Expanded Disability Status Scale (EDSS) scores between 1 and 7 were enrolled. Pre- and posttraining data from 36 participants (mean age ± SD, 46±11y; 30 women) who received training and 6 participants (mean age ± SD, 48±13y; 5 women) who did not receive training (control group) were compared. Interventions Five hours of driving training in a simulator. Main Outcome Measures Performance on a road test at pre- and posttraining. Secondary outcome measures were performance on visual, physical, and cognitive tests. Results Overall, no significant differences were observed between the training and control groups before and after training. However, 4 of the 7 participants in the training group who failed the road test at pretraining passed posttraining, while the only participant in the control group who failed at pretraining still failed at posttraining. The training group also improved on perception of red and colored numbers, the Paced Auditory Serial Addition Test, and the dot cancellation test of the Stroke Driver Screening Assessment battery and reported less fatigue. These improvements were most pronounced among those with an EDSS score between 3 and 7. Conclusions This pilot study demonstrates the potential of using a simulator to improve driving-related visual, cognitive, and on-road skills in individuals with RRMS, particularly those with an EDSS score >3. Future randomized controlled trials with adequate power are needed to expand this field of study.