PurposeThis study investigates the effectiveness of a new double-layer approach for closing oroantral and oronasal fistulas (OA/ONFs) using Matriderm® and Neoveil®. Matriderm®, an acellular dermal matrix composed of collagen and elastin fibers, supports tissue regeneration, while Neoveil®, a biodegradable mesh sheet, serves as a barrier to prevent leakage and scarring. Material and MethodsA retrospective study of 12 maxillectomy patients with oral cancer between January 2022 and May 2023 was conducted. Patient data, including tumor stage, bone invasion, and defect size, were analyzed. Surgical techniques included sinus mucosa preservation, and either buccal fat grafting combined with the double layer technique or the double layer technique alone, with statistical analysis performed using R software to evaluate outcomes. ResultsThe results indicate a 41.7% incidence rate of fistula formation with lower T stages, absence of bone invasion, smaller defect dimensions, and intact sinus mucosa correlating with reduced fistula risk (p < 0.05). Notably, no patients required fistula-related surgical revisions, validating the efficacy of the approach. ConclusionThis study introduced a novel double-layer technique using Matriderm® and Neoveil® for closing OA/ONFs after maxillectomy. The technique demonstrated promising outcomes in addressing these post-operative complications. Lower tumor stages, no bone invasion, smaller defects, and intact sinus mucosa correlated with reduced fistula risk. This technique holds potential to enhance maxillectomy outcomes, offering a comprehensive approach to functional concerns, but warrants further investigation.