Objective: We report favorable outcome after surgical decompression, or strokectomy, guided by xenon-enhanced computed tomographic studies of cerebral blood flow in the setting of potentially fatal swelling from massive cerebral infarction. Design: Retrospective analysis with 3 months to 3 years of follow-up. Setting: University of Pittsburgh (Pa) Medical Center, a tertiary care university referral center. Patients: Four patients, aged 14 to 46 years, presented with focal neurologic deficits appropriate for a massive middle cerebral artery infarction (two dominant and two nondominant). In spite of medical therapy, all patients deteriorated to at least a decreased level of consciousness. Intervention: Using xenon-enhanced computed tomographic studies of cerebral blood flow in three patients, areas of severely ischemic (blood flow, <5 ml/100 g per minute), nonviable brain were identified and resected. Outcome Measure: Outcome was measured by survival and ability to perform activities of daily living. Results: Postoperatively, all patients recovered rapidly (<6 hours) to the level of function at admission and were able to perform the activities of daily living with minimal or no assistance. Conclusion: Despite deficits appropriate to the area of infarction, prompt management of life-threatening postinfarction swelling by surgical decompression can yield favorable outcome.