Objectives/Hypothesis: The Caldwell-Luc operation for treatment of medically refractory chronic maxillary sinusitis has largely been replaced by functional endoscopic sinus surgery. Despite this change, the Caldwell-Luc procedure still has well documented indications including treatment of both failed endoscopic middle meatus antrostomy and irreversible mucosal changes. The purpose of the study was to review the authors' experience and results of Caldwell-Luc procedure after failed endoscopic middle meatus antrostomy in patients clinically deemed to have irreversible mucosal changes. Study Design: Retrospective review of preoperative and postoperative results of patients who underwent Caldwell-Luc procedure for refractory chronic maxillary sinusitis after failed endoscopic middle meatus antrostomy. Methods. The preoperative and postoperative clinical course of patients treated with Caldwell-Luc procedure performed by a single surgeon between 1996 and 2001 were reviewed. Only patients with a history of chronic sinusitis after failed maximal medical therapy, no prior Caldwell-Luc procedure, prior endoscopic middle meatus antrostomy, and at least 6 months of follow-up were included. Outcome measurements including documented endoscopic examinations and the need for repeat surgery, and postoperative computed tomography scan results were evaluated to assess treatment success. Results: The study involved 11 men and 26 women who underwent 50 Caldwell-Luc procedures. Caldwell-Luc procedure was performed bilaterally in 13 patients. The average number of prior endoscopic middle meatus antrostomies before Caldwell-Luc procedure was 2. Of all patients, 92% responded to surgical treatment as demonstrated by an endoscopic examination or computed tomography scan revealing a disease-free maxillary sinus. Repeat Caldwell-Luc procedure was required in 8.0% (n = 3) because of continued sinusitis. Two of the three cases with repeat Caldwell-Luc procedures demonstrated clinical improvement during follow-up. Average follow-up was 23.5 months. Conclusion: Caldwell-Luc procedure seems to be highly effective in the management of medically refractory chronic sinusitis after failed endoscopic middle meatus antrostomy. Caldwell-Luc procedure should remain in the otolaryngologist's surgical repertoire for these selected cases.