Direct cost associated with Multiple sclerosis: A Population-Based Study 1997-2017 Background: Multiple sclerosis (MS) is a chronic neurological disease often described as the most common disabling neurological condition among young people. There are limited studies around the burden of MS on Canadian society. The aim of this study is to explore healthcare resource utilization and estimate total direct cost and individual direct component costs attributable to MS. Objectives: The aim of this study is to explore healthcare resource utilization and estimate total direct cost of MS and important components. Methods: Using British Columbias administrative health data from 1997 to 2017, we created a cohort of MS patients who satisfied a validated case definition matched to a control cohort of individuals without MS. We applied a greedy matching algorithm to find five unique individuals matched on sex, age and cohort entry date for each MS patient. Each patient and his or her control were followed to the end of 2017 or their last healthcare resource use, whichever came first. We calculated direct medical cost (in 2017 Canadian dollars) for each patient during the follow up period based on billing records of outpatient service use, hospital admissions and dispensed medications. We used generalized linear models with an identity link and normal distribution to estimate the excess mean direct costs of MS from the differential direct costs of MS patients relative to their controls. Results: A total of15,083 patients fulfilled the case definition of MS and were matched to 75,415 individuals from the general population without MS. Mean age of both cohorts at entry was 45.3 (SD 13.1) years, 72.6% female, with a mean follow up time of 10.7 (SD 6.5) years. During the study period, the excess cost of MS was $5,055 (P<0.01) per patient-year, and the share of inpatient, outpatient, and medication was 31%, 14%, and 55% of total cost, respectively. Mean costs were $663 per patient-year higher among men at $5,380 compared with $4,717 (p<0.01) for women. Patients with a history of at least one relapse requiring hospital admission had much higher excess cost of $10,015 (p=0.01) per patient-year, and hospitalization accounted for 52% of the cost in this group. Conclusions: Medications and hospitalization costs are two main essential components of direct costs; an increase in either of these costs substantially affects the overall direct cost. While relapses increase costs of hospitalizations, using DMTs helps to slow disease progression, prevents relapses, and thus reduce costs of hospitalizations. Effective disease management strategies, including early diagnose of MS and proper treatment, may play an important role in reducing direct costs and improving patients quality of life.