Background: microRNA-494 (miRNA-494) plays a key role in neuroinflammation following cerebral ischemia. We aimed to assess miRNA-494 levels as a biomarker for predicting acute ischemic stroke (AIS) severity and outcomes.Methods: miRNA-494 levels in peripheral lymphocytes were measured using reverse transcription-quantitative polymerase chain reaction. Least Absolute Shrinkage and Selection Operator (LASSO) regression was employed to identify variables for multivariate logistic regression analysis. Univariate and multivariate logistic regression were conducted to assess the association between miRNA-494 levels and both AIS outcomes and stroke severity on admission. The primary outcome was defined as an excellent prognosis (modified Rankin Scale score of 0 or 1). The secondary outcome was milder stroke severity at admission (National Institutes of Health Stroke Scale score <15).Results: High miRNA-494 expression in patients aged <65 years predicted excellent AIS outcomes (odds ratio (OR) = 2.800 [1.120-7.002], p = 0.028, n = 105). In these patients, miRNA-494 levels predicted excellent outcomes for those who did not receive recanalization therapy (continuous: OR = 8.938 [2.123-62.910], p = 0.010; categorical: OR = 5.200 [1.480-20.773], p = 0.013). Elevated miRNA-494 levels were also linked to milder stroke severity (continuous: OR = 2.586 [1.024-6.533], p = 0.044; categorical variables: OR = 3.514 [1.501-8.230], p = 0.004, n = 205).Conclusions: Increased miRNA-494 expression in lymphocytes predicts excellent outcomes in patients aged <65 years with AIS. Higher miRNA-494 levels are associated with milder stroke on admission.