Background: The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment. Objectives: To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study. Design and Setting: Case studies at a university hospital. Interventions: Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment. Main Outcome Measures: National Institutes of Health Stroke Scale (NIHSS) score. Results: The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up. Conclusion: Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted. Background: The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment. Objectives: To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study. Design and Setting: Case studies at a university hospital. Interventions: Patients treated with intravenous thrombolytics within 3 hours of symptom onset succeeded underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment. Main Outcome Measures: National Institutes of Health Stroke Scale (NIHSS) score. Results: The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. complications. The NIHSS scores were 0 and 2 at 1-month follow-up. Conclusion: Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve results in acute stroke patients and a pilot safety trial is warranted.