Surgery and oral corticosteroids are recommended therapies for chronic rhinosinusitis with nasal polyps (CRSwNP) patients who are nonresponsive to intranasal corticosteroid treatment.This study aimed to compare the effectiveness of these 2 treatments in terms of improving sinus-related symptoms, enhancing quality of life, and economic costs and duration costs.This prospective study enrolled CRSwNP patients. All participants were instructed to complete the 22-item Sino-Nasal Outcome Test (SNOT-22), visual analog scale, and 36-item short-form (SF-36) questionnaire at baseline and 3 months after treatment. The nasal polyp score (NPS) was assessed via endoscopic examination. Additionally, patients were requested to maintain records of economic direct costs, other indirect costs, and duration costs throughout the 3-month period and to report them during each follow-up visit.A total of 40 patients who underwent surgery or received oral corticosteroids were enrolled in this study. After 3 months of treatment, significant improvements were observed between baseline and 3 months after treatment in the NPS, total SNOT-22 score, and nasal congestion, runny nose, facial pain, olfactory function, and overall symptoms measured. Only headache and sleep order were improved in the surgery group. Both physical functioning and general health, as measured by the SF-36, improved after both treatments, and the role-physical, bodily pain, and social functioning domains of the SF-36 improved only in the surgery group. The changes in the NPS, nasal congestion, runny nose, olfactory function, and sleep disorders in the surgery group were greater than those in the oral corticosteroid group (P values = 0.0003, 0.0092, 0.0258, 0.0284, and 0.0164, respectively). Changes in the total SNOT-22 score and SF-36 subscores were not different between the 2 treatment groups. The direct economic costs and duration costs of surgical treatment were 4.5 times and 17.0 times higher, respectively, than those of oral corticosteroid treatment.Both surgical and oral corticosteroid treatments effectively improved clinical symptoms and quality of life in patients with CRSwNP. Patients who underwent surgery exhibited greater improvements in sinus-related symptoms. Nevertheless, oral corticosteroid treatment presented notable advantages in terms of economic cost and duration cost of disease-related care.Copyright © 2024. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.