OBJECTIVEIn this study, we aimed to determine whether insulin resistance is associated with clinical outcomes after acute ischemic stroke. METHODSWe enrolled 4,655 patients with acute ischemic stroke (aged 70.3 ± 12.5 years, 63.5% men) who had been independent before admission; were hospitalized in 7 stroke centers in Fukuoka, Japan, from April 2009 to March 2015; and received no insulin therapy during hospitalization. The homeostasis model assessment of insulin resistance (HOMA-IR) score was calculated using fasting blood glucose and insulin levels measured 8.3 ± 7.8 days after onset. Study outcomes were neurologic improvement (≥4-point decrease in NIH Stroke Scale score or 0 at discharge), poor functional outcome (modified Rankin Scale score of ≥3 at 3 months), and 3-month prognosis (stroke recurrence and all-cause mortality). Logistic regression analysis was used to evaluate the association of the HOMA-IR score with clinical outcomes. RESULTSThe HOMA-IR score was associated with neurologic improvement (odds ratio, 0.68 95% confidence interval, 0.56–0.83, top vs bottom quintile) and with poor functional outcome (2.02 1.52–2.68, top vs bottom quintile) after adjusting for potential confounding factors, including diabetes and body mass index. HOMA-IR was not associated with stroke recurrence or mortality within 3 months of onset. The associations were maintained in nondiabetic or nonobese patients. No heterogeneity was observed according to age, sex, stroke subtype, or stroke severity. CONCLUSIONSThese findings suggest that insulin resistance is independently associated with poor functional outcome after acute ischemic stroke apart from the risk of short-term stroke recurrence or mortality.