Higher admission glucose levels (AGL) are associated with less favorable outcome in thrombolysis. But, could AGL’s impact on outcome vary by onset-to-treatment (OTT) time? Is hyperglycemia associated with a shorter therapeutic time window for excellent outcome for thrombolysed stroke patients? We assessed predictive values of AGL, baseline NIHSS, age, and OTT time quartiles on excellent outcome (3-month modified Rankin score of 0–1) in 773 patients treated by rt-Pa. We added the AGL × OTT time quartile interaction in the model and separately analyzed the predictive values of AGL, age, and NIHSS for each OTT time quartile if the interaction was significant. AGL, baseline NIHSS, age, and OTT time quartiles were significant predictors. When added in the model, the AGL × OTT interaction was significant (OR: 0.96, 95% CI: 0.94–0.99, p: 0.0009). AGL was predictive only during the third OTT time quartile (181–224 min). During this period, the predicted rate of excellent outcome was 16% for AGL = 6.5 mmol/L and 8% for AGL = 8 mmol/L. The rate of excellent outcome was not decreased in hyperglycemic patients for OTT time ≤ 180 min (20 vs. 24.5% p: 0.37), but was decreased for OTT time > 180 min (9.6 vs. 26.7% p: 0.00001). Similar results were found in patients with MCA recanalization, but not in patients without recanalization. The therapeutic time window for excellent outcome is shortened in hyperglycemic patients. This would support the design of “freezing penumbra” randomized trials based on ultra-early AGL control.