Background: An increasing trend has been observed in the prevalence of Multiple Sclerosis (MS) globally. It is estimated that a total of 2.8 million people live with MS worldwide. In 2008, Chile started a pilot program for the Modifying Therapy of MS, and its clinical practice guideline. Aim: This study aims to analyze the trend of the MS mortality rate in Chile from 1997 to 2019 disaggregated by sex and latitude. Methods: MS mortality data (ICD-10, G35) from 1997-2019 were extracted from the Department of Health Statistical Information and population data from the National Institute of Statistics. Standardized mortality rates (SMRs) by age were calculated. The trend of the SMR was analyzed using Joinpoint and with RiskDiff the effect of the risk of dying, the structure, and the size of the population on the crude mortality rate was evaluated. Results: The trend of the TME has been decreasing significantly since 2005. When disaggregating by sex the decrease was not significant. According to latitude, the north and center south have a significant decreasing trend; in the south, the decreasing trend is not significant. There is an increase of 25% in the crude mortality rate due to the change in the structure of the population and a decrease of 25.46% is attributed to the risk of dying. Conclusion: The SMR due to MS in Chile during 1997-2019 has decreased, in addition, a decreasing SMR is evidenced only in the northern zone. The crude rate has increased as a consequence of changes in the population, however, the risk of dying has decreased, especially in men.