The present study evaluated the hemostatic efficacy and handling of gelatin-thrombin matrix hemostatic sealant during intracranial procedures. A retrospective analysis of 478 consecutive patients undergoing intracranial procedures identified seven patients with acute intense or persistent intraoperative bleeding which could not be arrested in time by standard hemostatic methods. The efficacy of gelatin-thrombin matrix was assessed by determining bleeding severity before and after application, time to hemostasis, amount of gelatin-thrombin matrix necessary, need for additional hemostatic measures, and need for reoperation to control hemorrhage. Immediate hemostasis was achieved in five of seven patients. Two of these five patients had abnormal clotting parameters. Cessation of bleeding was achieved by additionally applying either fibrinogen or gelatin sponge to the bleeding site in the other two patients. No complications attributable to gelatin-thrombin matrix use were recorded. The gelatin-thrombin matrix was ready to use within 1 minute in every case. Gelatin-thrombin matrix appears to be an effective, easy-to-use, and readily available hemostatic agent for cranial neurosurgery. Combination with fibrinogen is recommended in special situations.