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Background: Seasonal variation in stroke occurrence and outcomes has been reported in small populational studies but the significance of a seasonal effect is uncertain. The important patient and climate variables underlying this phenomenon have not yet been identified.Methods: Using Get With The Guidelines-Stroke data from 2011 to 2015, we studied 457,638 consecutive ischemic stroke patients at 896 sites. We calculated the relative prevalence of acute stroke admissions in each season. Baseline characteristics and discharge outcomes were compared across seasons and the effects of season, climate region (as defined by the National Climatic Data Center), and climate variables on outcomes were analyzed using logistic regression. In secondary analyses, odds ratios were calculated for various outcomes.Results: Among all cases of ischemic stroke, there was significant difference in the frequency distributions of cases across seasons (p<.0001), with the highest percentage of strokes occurring in winter (25.5%). Across seasons, winter patients had the highest percentage of atrial fibrillation (17.7%), longest median time to arrival (202 minutes), highest in-hospital mortality (4.4%), and most discharge mRS scores > 3 (43.7%). P<.0001 for all the above. Higher precipitation and temperature were associated with reduced mortality independent of climate region or season (OR .93, CI .89-.97, p=.0005 and OR .97, CI .97-.98, p<.0001, respectively). Odds ratios for in-hospital mortality are summarized in the accompanying table.Conclusions: More patients presented with acute ischemic stroke in winter relative to other seasons, accompanied by trends toward poorer outcomes. Although an association with mortality was seen for winter in our unadjusted analysis, confounding variables likely exist. Precipitation and temperature were independently associated with stroke mortality.