Background: Inconsistent evidence supports better outcome in smokers after stroke. Our study examines this association in a large sample of ischemic stroke treated with intravenous thrombolysis. Method: Virtual International Stroke Trials Archive (VISTA) database, composed of individual patient data of multiple clinical trials, was queried. The primary outcome was functional independence at 3 months noted by modified Rankin Scale (mRS; a 7-point scale ranging from 0 [no deficit] to 6 [death]) score/= 65 years. Current smoking was also associated with lower rates of symptomatic intracranial hemorrhage (adjusted OR 0.55, 95% CI 0.39-0.79). Conclusion: Smokers experience their first ever stroke 11 years younger than nonsmokers. This age difference explains the association between current smoking and favorable functional outcome. Implications: Smoking is associated with occurrence of first ever stroke at a younger age, therefore, focus should be on smoking prevention and treatment. The decision to treat ischemic stroke patients with intravenous thrombolysis should not be influenced by the patients' smoking status.