Background and Purpose: A hub and spoke model for telestroke has been increasingly utilized for the treatment of acute ischemic stroke (AIS) with intravenous recombinant tissue plasminogen activator (IV rtPA). We aimed to compare the outcomes of IV rtPA therapy in patients with AIS between hub and spoke hospitals. Methods: We retrospectively investigated consecutive 203 patients with AIS following IV rtPA treatment between April 2012 and October 2021 using medical records from an ongoing stroke registry at our institution. The patients were classified as the islands group (transfer using the drip/ship method from spoke hospitals) and the mainland group (direct transfer to the hub hospital). We analyzed the patient characteristics and outcomes between the two groups. Results: Among 203 rtPA-treated patients, all the patients in the islands group (61 cases=30.0%) were transferred to the hub after IV rtPA treatment. No significant differences between the two groups were seen in patient characteristics, rates of symptomatic intracranial hemorrhage, and a good functional outcome (mRS, 0–2) at 30 days. No patient underwent hematoma evacuation. Conclusion: No differences were noted in patient outcomes between the hub and spoke hospitals. Our findings indicated that the IV rtPA use via telestroke at spoke hospitals was safe, and patient transportation to the hub for post-rtPA care may not always be necessary.