Introduction: AERD (aspirin-exacerbated respiratory disease) is a severe form of an inflammatory disease of the upper airway system. Therapy remains challenging due to a complex underlying pathophysiology. Objective: To evaluate the efficacy of postoperative antileukotriene therapy concerning recurrence of nasal polyposis in patients with AERD and to compare it with AD (aspirin desensitization) over time. Methods: In this retrospective study we analyzed AERD patients (N = 61) after functional endoscopic sinus surgery (FESS). Patients were treated at our institution postoperatively with topical mometasone (control group, N = 22), leukotriene-receptor-antagonists (montelukast [MT], N = 18) or underwent an aspirin desensitization (N = 21). Subjective parameters as assessed by SNOT (sinonasal outcome test) questionnaire and endoscopic endonasal examination (polyposis grading) were evaluated throughout a follow-up period of 6–9 and >12 (long-term) months after surgery. Results: Endoscopic endonasal examinations 6–9 months after sinus surgery showed a good disease control in all 3 groups with significant reduction in polyp grading in the AD group. After a follow-up period of more than 12 months, MT and AD patients had significantly less polyp recurrences as compared to the topical treatment group. Subjective sinonasal symptoms revealed that hyposmia and nasal obstruction were prominent factors in all 3 groups throughout the follow-up period. MT group showed significant improvement in sinonasal symptoms over time. Conclusion: Postoperative treatment with leukotriene-receptor-antagonists and aspirin desensitization both significantly reduce nasal polyp recurrence. MT has a positive effect on subjective sinonasal outcomes and patients’ quality of life over time.