Objective: To assess the opinions of persons with multiple sclerosis (MS) regarding physician-assisted death (PAD). Methods: We surveyed participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding PAD. For each of 5 hypothetical situations, respondents indicated whether they definitely would, probably would, probably would not, or definitely would not consider PAD. They also reported their sociodemographics, disability status using Patient-Determined Disease Steps, depression status, pain status, religiosity, and degree of social support. Using multivariable logistic regression models, we evaluated the factors associated with an individual reporting that he or she would definitely or probably consider PAD in each situation. Results: Of 7,534 respondents, 6,011 (79.8%) were female, and 6,884 (92.9%) were white. Their mean (SD) age was 59.9 (10.2) years. Fifty percent of respondents reported at least moderate disability. Of the 6,792 respondents who responded to any of the PAD questions, 6,400 responded to all questions. Of these, 458 (7.1%) indicated that they would definitely consider PAD in all of the situations listed, while 1,275 (19.9%) indicated that they definitely would not consider PAD in any of the situations listed. If experiencing unbearable pain, 4,383 (65.3%) of respondents would definitely or probably consider PAD. On multivariable analysis, religiosity, social support, depression, pain, disability, sex, and race were associated with considering PAD in some or all of the situations presented. Conclusions: Depending upon the situation, a large proportion of persons with MS would consider PAD. The association of depression with considering PAD emphasizes the importance of diagnosing and treating depression.