INTRODUCTION: Population-based longitudinal data on mortality and causes of death (COD) for people with Multiple Sclerosis (pwMS) is scarce. We studied all-cause and cause-specific mortality in Finnish pwMS in a nationwide registry study. METHODS: PwMS from 1st January 1971 until end of 2019 were identified from the Finnish MS registry and national health care register. Standardized mortality ratios (SMRs), excess death rates (EDRs), life expectancies, and causes of death (COD) were determined by linkage to national registries. RESULTS: For 16,602 pwMS, 3936 deaths occurred between 1980 and 2020. During 1980-1999, SMR for pwMS was 3.07 (95% CI 2.91-3.25) and EDR 14.05 (95% CI 13.72-14.37), and during 2000-2020 2.18 (95% CI 2.10-2.26) and 7.48 (95% CI 7.2-7.75), respectively. SMRs were higher for female pwMS and for patients diagnosed under age 30. EDRs were higher for males. Risk of death was lower for pwMS diagnosed 1996-2005 versus 1980-1995 (HR 0.49
95% CI 0.43-0.55
p <
0.002). MS was the underlying cause in 51.2%, and a mentioned cause in 73.1% of deaths during 2000-2020. Mortality by underlying cause was higher than expected for gastrointestinal diseases (SMR 2.15, 95% CI 1.53-2.77), respiratory infections (SMR 1.99, 95% CI 1.22-2.75), and vascular diseases (SMR 1.38, 95% CI 1.25-1.51). Median lifetime expectancy was shortened by 7 years. CONCLUSION: Excess mortality in Finnish pwMS has decreased during the last 40 years. Life expectancy is shortened by 7 years and MS itself is the most frequent underlying COD. Risk of death is lower for pwMS diagnosed during the therapeutic era.