Background Nasal septal perforation repair remains a challenge with no standard technique for repair recognized. Objective To describe the combination of an anterior ethmoidal artery flap with a collagen matrix inlay as a successful technique for nasal septal perforation repair. Methods A case series of consecutive patients who underwent nasal septal perforation repair with an anterior ethmoidal artery flap with an inlay collagen graft was conducted. Demographic data, preoperative features of the perforation (size, location, and presence of chondritis), and postoperative outcomes were analyzed; closure rate, mucosalization rate (of the contralateral side at 21 and 90 days), and complications (crusting, bleeding, obstruction, infection, and rehospitalization <30 days) were documented. Results Thirteen patients (age: 49 ± 15 years, 30.8% women) were assessed. The perforation size was 1.6 ± 0.9 cm (range: 0.3–3.5 cm) and located 1.2 ± 0.5 cm (range: 0.5–2.0 cm) posterior to the columella. Chondritis was present in 69.2%. The closure rate was 100% (95% confidence interval [CI]: 77%–100%) at both 21 and 90 days. One patient required a free mucosa graft to an area of persistent crusting on the contralateral side (7.7%). Complications were low; bleeding 0%, obstruction 7.7% (requiring corticosteroid injection of anterior ethmoidal artery flap), and 0% infection/rehospitalization. Conclusion Anterior ethmoidal artery flap with an inlay collagen matrix is a reliable technique to repair nasal septal perforation. This technique, with robust vascularity and wide angle of rotation, enables the closure of perforations both large (<50% total septum) and with anterior locations.