BACKGROUND: Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is a prevalent chronic inflammatory disorder of the nasal cavity and paranasal sinus with benign polypoid masses. Recent evidence highlights the immunomodulatory role of Vitamin D (Vit D) in mitigating inflammation associated with CRSwNP. AIMS: The aim of this study is to examine the effect of Vit D on the improvement of CRSwNP. MATERIAL AND METHODS: This randomized, double-blind clinical trial was conducted on 59 patients with CRSwNP. All patients with Vit D deficiency (25OH Vit D level <
20 ng/mL) or insufficiency (<
30 ng/mL) underwent endoscopic sinus surgery (ESS). The rate of changes in the patients' symptoms were recorded before and 8 weeks after the surgery. RESULT: All patients showed a better postsurgical improvement in terms of Visual Analogue Scale(VAS), Lund-Kennedy (LK), and Questionnaire (SNOT-22) scores. The Vit D supplement group showed better postsurgical improvement in comparison to placebo in terms of VAS and LK scores ( CONCLUSIONS AND SIGNIFICANCE: The administration of Vit D after ESS is relatively effective in the improvement of CRSwNP symptoms. This finding highlights the possibility of developing an efficient, safe, and cost-effective therapy for patients with CRSwNP.