Background: Primary total laryngopharyngectomy is the treatment of choice in many cases of locally advanced hypopharyngeal and laryngeal cancer. Development of pharyngocutaneous fistulae is the most common postoperative complication. A recent Danish study showed significantly increased rates of anastomosal leakage after colorectal resection in patients receiving diclofenac treatment., Methods: We retrospectively analyzed 67 patients after primary total laryngopharyngectomy to determine whether diclofenac increases the risk for development of pharyngocutaneous fistula analogously to leakage in the colorectal area., Results: The fistula rate in the total study population (n = 67) was 19.4%. In the group receiving diclofenac postoperatively (n = 31), the fistula rate was 25.8%. In the patient group not receiving diclofenac (n = 36), the fistula rate was 13.9% (p = .219)., Conclusion: Our results suggest that cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) should be administered with caution after laryngopharyngectomy. Additional studies on larger cohorts are required to further evaluate our findings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1515-E1520, 2016., (© 2015 Wiley Periodicals, Inc.)