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Background: While several studies have evaluated healthcare costs of stroke, limited data are available on long-term costs by stroke severity.Objective: To assess healthcare costs in relation to stroke severity over 3 years following stroke diagnosis.Methods: Patients with newly diagnosed stroke were assessed using OPTUM de-identified Integrated Claims-Medical Record Database (2007-2016). The National Institutes of Health Stroke Scale (NIHSS) score, imputed by 100 clinically relevant predictors selected by a random forest method, was used to group patients by severity: no impairment (<1, NI), minor (1-5, Min), moderate (>5-16, Mod), moderately severe (>16-21, MS), severe (>21-42, S). All-cause medical and pharmacy costs were estimated in patients for up to 3 years following diagnosis. Mean cumulative costs were evaluated by partitioning the follow-up period into 2-week intervals. The average cost incurred in each interval was then weighted by the Kaplan-Meier survival probability at the beginning of each interval, after which costs were summed across all intervals.Results: We identified 8512 patients with a mean age of 69 years at first stroke diagnosis; 1396, 4783, 1927, 215 and 191 were in the NI, Min, Mod, MS, and S cohorts, respectively. Mortality was 3%, 13%, 33%, 88% and 100% at Year 3 following stroke diagnosis in the NI, Min, Mod, MS, and S cohorts, respectively. In year 1 following diagnosis, the cumulative total healthcare costs were the highest in the Mod cohort (mean ± SE; $67365±$1234) and lowest in the S cohort ($15945±$647). Healthcare costs increased in year 3 substantially compared to year 1, with the NI cohort showing the greatest increase in healthcare costs (116% increase), followed by the Min (86%), Mod (39%), MS (9%) and S (0%) cohorts. Hospitalization was the costliest healthcare service across all cohorts and ranged in Year 3 from $62100 in the Mod cohort to $13241 in the S cohort; outpatient services were the second most costly.Conclusion: Majority of patients with severe strokes (MS and S) incurred high healthcare costs within a month whereas patients with less severe strokes (Min and NI) accrued more costs over time due to better survival outcomes, underscoring short and long-term economic burden of various degrees of stroke severity.