Background - The objective of our study was to describe regional disparities in 30-day mortality (early mortality) following hospitalization for ischemic stroke in mainland France. Method - Data were extracted from the National Health Data System (SNDS). For each year from 2013 to 2015, patients hospitalized for ischemic stroke aged 18 years or older, enrolled in the general health insurance scheme, and residing in mainland France were selected based on I63 codes from the International Classification of Diseases, 10th Revision (ICD-10). Age- and sex-standardized case-fatality rates were calculated by department. The interdepartmental variability of these rates was analyzed using multivariate logistic regression models with mixed effects and a random constant per department. Results - At the national level, the 30-day mortality rate among the 163,596 patients hospitalized for ischemic stroke between 2013 and 2015 was 10.4%. Standardized early mortality rates varied across departments from 8.1% (Paris) to 14.2% (Vosges). Age, the presence of motor deficits, comorbidities, a history of stroke, use of antihypertensive medication, socioeconomic disadvantage, as well as the density of neurovascular intensive care unit (NVICU) beds and admission to these units accounted for 43% of the variability between departments. After accounting for these factors, variability remained significant. While some departments maintained a low case fatality rate (Finistère, Moselle, Maine-et-Loire, Ille-et-Vilaine, Haute-Garonne, and Manche) or high (Vosges, Alpes-Maritimes, Var, Seine-Maritime, and Dordogne) after all adjustments, others saw their mortality rates shift toward higher or lower mortality after adjustment. Conclusions - Significant interdepartmental disparities in 30-day mortality following hospitalization for ischemic stroke were identified in metropolitan France. One-quarter of the interdepartmental variability in 30-day mortality was explained by individual factors and 17% by differences in care, particularly admission to the stroke unit, with the remainder of the variability remaining unexplained.