Severe dry eyes often require surgical intervention. Submandibular salivary and minor salivary gland transplantation are options for refractory dry eyes but have limitations. We innovatively designed an insular infraorbital neurovascular pedicle labial salivary gland transplantation (IINPLSGT) and validated its feasibility and safety through anatomical studies.An anatomical study was conducted on 13 red-colored latex arterial-perfused cadavers (24 sides). Two specimens (4 sides) simulated IINPLSGT. We recorded the branching patterns and courses of the infraorbital artery, infraorbital nerve, and angular artery, as well as the distribution of nerves, vessels, and salivary glands in the upper lip. Infraorbital artery and angular artery were anatomically classified. The feasibility of the IINPLSGT was validated. Otolaryngologists and ophthalmologists performed IINPLSGT, transferring the labial mucosal flap to the lower eyelid conjunctival fornix to treat severe dry eye in 1 patient.Infraorbital artery exhibited 5 potential branches, classified into 5 types based on developmental patterns. Angular artery was classified into 3 types based on the courses. Patient symptoms significantly improved postoperatively, with Schirmer I increasing from 0 mm to 6 mm, noninvasive breakup time from 0 seconds to 6 seconds, and SPEED (Standard Patient Evaluation of Eye Dryness questionnaire) score decreasing from 10.5 to 3 in the OD 1 year after surgery. No severe complications were observed.IINPLSGT is a safe and feasible method for treating severe dry eyes. The procedure is simple, with a high postoperative gland survival rate, stable secretion, and minimal complications.Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.