Cigarette smoking is the leading preventable cause of death and disease among adults, and there is evidence that smokers with multiple sclerosis (MS) are at an increased risk for accelerated disease conversion and progression toward disability. Recent research has shown resistance training (i.e., weight training) to be beneficial for smoking cessation in the general population; however, no study has examined the use of resistance training as an aid to cessation in those with MS. Methods: After receiving brief smoking cessation counseling and the nicotine patch, smokers with relapsing-remitting MS will be randomized into a Resistance Training (RT) or Contact Control (CC) group. Participants in the RT group will attend a 60-minute resistance training session twice weekly for eight weeks, while participants in the CC will attend a 30-minute health education control session twice weekly for eight weeks. Measurements will be taken at baseline, weekly during the intervention, at the end of the eight-week study period, and at a one-month follow-up. The primary outcome will be smoking cessation, indicated by a 7-day abstinence, and verified by biochemical assay (i.e., carbon monoxide breath test). Secondary outcomes will include other smoking-related variables (e.g., nicotine withdrawal symptoms), multiple sclerosis-related factors (e.g., fatigue), and physical assessments (e.g., muscular strength). Discussion: The results from this study will lay the foundation for subsequent tests of the intervention in smokers with MS, with the long-term goal of providing specific recommendations and guidelines for smoking cessation that can be integrated into the clinical care of persons with MS. © 2012.