Background: Interest in and use of marijuana by persons with multiple sclerosis (MS) has increased. While potential benefits have been reported, so have concerns about potential risks. Few large studies have been conducted about the perceptions and current usage of marijuana and medical cannabinoids in persons with MS. Methods: Participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry were surveyed in 2014 regarding legality and history of marijuana usage, both before and after diagnosis with MS. Results: A total of 5,481 participants responded, with 78.2% female, 90% relapsing disease at onset, and a current mean age of 55.5 (10.2) years. Sixty-four percent had tried marijuana prior to their MS diagnosis, 47% have considered using for their MS, 26% have used for their MS, 20% have spoken with their physician about use, and 16% are currently using marijuana. Ninety-one percent think marijuana should be legal in some form. Men, those with higher disability, current and past nicotine smokers, and younger age were associated with a higher likelihood of current use. Conclusions: The majority of responders favor legalization and report high interest in the use of marijuana for treatment of MS symptoms, but may be reluctant to discuss this with health care providers. Health care providers should systematically inquire about use of marijuana.