Mucosal preservation is paramount to achieving successful outcomes after endoscopic sinus surgery (ESS). Despite best surgical practices and implementation of evidenced-based postoperative care, patients in rare cases might exhibit persistent demucosalization that is recalcitrant to conservative therapies. We retrospectively reviewed the records of 3 patients-a 63-year-old woman, a 67-year-old woman, and a 43-year-old man-who experienced clinically significant local demucosalization after uncomplicated ESS despite routine surgical and postoperative management. We collected data on the characteristics of presentation, wound management strategies, and postoperative care practices. Two patients achieved remucosalization with mechanical debridement, gelatin sponge placement, and intensive moisturization therapy. Our experience suggests that surgical debridement of these chronic, persistent demucosalized wounds may be an effective management strategy for patients who develop this unusual and rare postoperative complication. Biopsy and culture of the persistently demucosalized wound bed may be useful in recognizing the presence of worrisome disease processes and identifying any tenacious infectious agents so that more appropriate therapy can be initiated if necessary.