ObjectiveTo determine tolerance to various risk scenarios associated with current multiple sclerosis (MS) therapies.MethodsPeople with MS from the North American Research Committee on Multiple Sclerosis Registry's online cohort and the National Multiple Sclerosis Society were invited to complete a questionnaire on tolerance to real-world risks associated with a hypothetical therapy. Multiple risks levels were presented, including skin rash, infection, kidney injury, thyroid injury, liver injury, and progressive multifocal leukoencephalopathy (PML).ResultsBoth PML and kidney injury had the lowest risk tolerance (RT) at 1:1,000,000, and thyroid and infection risks had the highest tolerance at 1:1,000. Men, younger individuals, and participants with greater disability reported a higher tolerance to all risk scenarios. Those who were currently taking an MS therapy reported higher tolerance than those not taking any therapy. Participants taking infusion therapies reported high tolerance to all risks, and those taking injectables reported a lower tolerance.ConclusionPeople with MS displayed a wide range of RT for MS therapies. Our study identified sex, age, disability, and current disease-modifying therapy use to be associated with RT.