Background: Postoperative infection remains a serious complication after radical resection of anterior skull base lesions because intracranial, nasal, and paranasal cavities are opened during surgery. To prevent complications from postoperative infection, we combined endonasal endoscopic sinus surgery (ESS) with the frontal transbasal approach in patients with skull base lesions. Methods: Patients (n = 16) with anterior skull base lesions extending to the paranasal or nasal cavity underwent surgical resection via the frontal transbasal approach. After removal of the lesion via the transcranial approach, enlargement of the ostium or sinusotomy was performed bilaterally using our endonasal ESS procedure. The main purpose of ESS is the establishment of a wide drainage route to avoid dead space and postoperative infection. Furthermore, we confirmed the absence of residual lesion and leakage of cerebrospinal fluid (CSF), endoscopically. Results: The frontal transbasal approach combined with endonasal ESS was performed in 16 patients with frontal skull base lesions. There were 8 malignant tumors, 6 benign tumors, and 2 mucoceles. Although 11 patients had preoperative active paranasal sinusitis, most frequently at the ethmoid sinus, none experienced postoperative infection. There was no complication related to ESS procedure. Furthermore, leakage of CSF and extracranial residual tumor were not found. Conclusion: Endonasal ESS after frontal skull base surgery is a highly useful technique for preventing postoperative infection, especially for the cases with large skull base tumors extending into other regions involving the paranasal sinuses or nasal cavity and with active paranasal sinusitis.