Objective: to study the effect of smoking on immediate clinical and functional outcome after intravenous thrombolysis for treatment of acute ischemic stroke. Background: “Smoker’s paradox” is a term first coined to describe the counterintuitive observation of better outcomes in smokers than non-smokers following acute myocardial infarction. Similar observation was made after ischemic stroke and attributed to differences between smokers and non smokers in demographic and risk factor characteristics, in favor of smokers. However, other studies showed an independent effect of smoking on recanalization. Method: using the Virtual International Stroke Trials Archive (VISTA), we identified patients who had ischemic stroke and were treated with intravenous thrombolysis (IVT). Smokers and never-smokers were identified. Univariate and multivariate analysis performed to identify correlation with good clinical (drop of National Institutes of Health Stroke Scale, NIHSS, of 4 or more points) and good functional (modified Rankin Scale, mRS) outcomes. Results: 9215 patients were identified. 1994 (22[percnt]) smokers and 5529 (60[percnt]) never smokers. Ex smokers 1692 (18.36[percnt]) were excluded. Smokers were younger, had less female gender, had less frequent hypertension and atrial fibrillation, but more frequent diabetes and heart failure. Smokers had lower initial mean NIHSS (12.7 vs 13.4), and at 24 hours (9.9 vs 10.9), however, smoking did not predict neurological improvement after correcting for age, gender, and initial NIHSS (odds ratio 0.9, 95[percnt] confidence interval 0.8-1.05). mRS was not different at 30 days or 90 days between the two groups. Conclusion: There is no smoker's paradox in ischemic stroke.