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CSF leak still is one of the major sources of morbidity after extensive skull base procedures. Of the various standard closure techniques of traumatic or iatrogenic dural defects, none provides a really waterlight, persistent closure. Even the supplementary use of fluid fibrin glue did not substantially improve the rate of postoperative CSF leaks. The application of a collagen sheet covered with a fixed layer of solid components of a fibrin tissue glue (TachoComb®) overcomes the major drawbacks of dural sealing in skull base surgery. The dural defects of 58 patients undergoing extensive skull base procedures were sealed with this new hemostyptic agent. The series includes 44 patients undergoing primary surgery, 6 patients with traumatic or iatrogenic tears of venous sinuses, and 8 patients with postoperative leaks after previous skull base procedures in which other sealing methods were previously used. In the group of primary surgery, none of the patients had postoperative CSF leakage or venous rebleeding. One patient developed a delayed pneumatocephalus. All cases of patent CSF fistulas were resolved without any adjuvant therapy. Preliminary experience shows that the good sealing and hemostyptic performance of this new agent will considerably reduce the risk of postoperative CSF leak and infection after skull base procedures.