Aim: To evaluate the predictive value of cerebral oximetry for functional recovery in patients undergoing reperfusion therapy for ischemic stroke.Materials and Methods: A post hoc analysis was performed using data from a single-center, open-label, randomized controlled trial. The study included 45 patients with ischemic stroke who received systemic thrombolysis. Primary outcomes included functional recovery as assessed by modified Rankin Scale and mortality. Serial cerebral oximetry was performed within the first 24 hours after thrombolysis. The interhemispheric difference (IHD) in cerebral oximetry was used to determine a cutoff point for predicting functional recovery using ROC curve analysis. Associations between IHD and outcomes were analyzed using univariate and multivariate logistic regression models.Results: The IHD in cerebral oxygenation between the unaffected and affected hemispheres was 4% (3-5%) before thrombolysis and dropped to 3% (1-4%) 24 hours after thrombolysis (P = 0.024). An IHD of less than 4% was identified as an independent predictor of favorable functional outcome with an adjusted odds ratio of 12 (95% CI: 1.6-93.7; P = 0.017). However, IHD less than 4% was not predictive of mortality (P = 0.301).Conclusion: Systemic thrombolysis in ischemic stroke is associated with improved cerebral oxygenation. An IHD in cerebral oxygenation of less than 4% serves as an independent predictor of favorable functional recovery in ischemic stroke patients but does not correlate with reduced mortality.