Background: Early and accurate prediction of outcome in acute stroke is important. The aim of this prospective study was to explore the correlation between serum triiodothyronine level and prognosis in acute ischemic stroke patients. Methods: A prospective observational study which included 359 consecutive patients with acute ischemic stroke from December 2014 to November 2015 was interrogated. Serum triiodothyronine (T-3) concentrations were measured on admission to understand their value in predicting functional outcome within 90 d using multivariable models adjusted for confounding factors. Receiver operating characteristic (ROC) curves were calculated to define the best cut-off value of triiodothyronine to predict outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC). Results: Triiodothyronine was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome within 90 d (p = 0.01). Binary logistic regression analyses revealed that lower triiodothyronine concentrations on admission were associated with a risk for poor outcomes (OR 0.05, 95% CI 0.01-0.25; p < 0.01). In addition, in ROC curve analysis, triiodothyronine may improve the National Institutes of Health Stroke Scale (NIHSS) score in predicting functional outcome. The combined model AUROC was 0.84 for 30 d and 0.91 for 90 d, which were both significantly higher than the AUROCs of original NIHSS (0.83 and 0.87), triiodothyronine (0.64 and 0.69) and age (0.57 and 0.68) (all p < 0.05). Conclusions: Low serum triiodothyronine levels can be a predictive marker of short-term outcome after ischemic stroke. A combined model (triiodothyronine, age and NIHSS score) can add significant additional predictive information to the clinical score of the NIHSS.