IntroductionMultiple sclerosis (MS) is an autoimmune disease that can be disabling to patients. Smoking has been proposed to be a risk factor for MS and to increase the risk of progression of the disease and its severity. However, it is still not clear how smoking affects people with MS (PwMS) regarding disease phenotype, symptoms, relapses, course, and disability. The aim of this study is to investigate the effect of smoking on PwMS in Saudi Arabia.MethodsThis is an online questionnaire-based cross-sectional study. PwMS were randomly contacted through different MS societies and associations to participate in the study. The questionnaire inquired about demographics, MS phenotype and severity, and smoking status of the participants. Data were collected between May 30, 2021, and July 5, 2021.ResultsFour hundred twenty-nine PwMS participated in the study. The mean age was 33.7, with a mean disease duration of 8.1 years. About 61.1% of the participants were female. About 62.2% did not know the specific MS phenotype they have. About 35.7% were current or previous smokers, with a mean smoking duration of 13.9 years. Smoking was significantly associated with the presence of multiple MS symptoms (p-value = 0.009) and their number (p-value = 0.050). In addition, there was a significant positive correlation between pack-years smoking and the number of MS symptoms with a Pearson's r value of 0.165 (p-value = 0.001). No significant associations were found between smoking and recent relapses and disease progression, disability in terms of walking, needing a cane, or needing a wheelchair.ConclusionSmoking was shown to have a significant effect on the number of symptoms experienced by PwMS. Higher pack-years of smoking correlates positively and significantly with a higher number of MS symptoms. Further studies to examine these relations are hence warranted.