Atrial fibrillation (AF) is associated with rapid ventricular response (RVR) that increases myocardial demand and blood pressure instability. We investigated the incidence, risk factors, and outcomes of RVR among patients with ischemic stroke receiving treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA). Consecutive patients with AF who received IV rtPA within 3 hours of symptom onset were included. Vascular risk factors, stroke characteristics, and outcome measures were compared between patients who developed RVR and those who did not. Eighty patients with AF (mean age, 79 years; 46% men) who underwent rtPA treatment were studied. Nineteen (24%) of these patients developed RVR and were treated with IV rate-controlling medications. A bimodal pattern of distribution was observed in the occurrence of RVR, with the first peak occurring within 12 hours of stroke onset and the second peak occurring 24-48 hours after onset. Compared with the patients without RVR, those with RVR stayed a median duration of 1.2 days longer in the intensive care unit (P = .048). There were no differences in functional recovery and hemorrhagic outcomes between the patients with RVR and those without RVR. We observed a 16-hour delay in the resumption of antiarrhythmic medications (either at previous or reduced dosage) in the patients who subsequently developed RVR (median time from stroke onset, 29 hours vs 13 hours; P = .040). Our findings suggest that a delay in the resumption of rate-control medications in patients with AF may result in RVR and prolong the use of intensive care resources.