Background: Nasal polyp (NP) is the most common benign tumor that can cause nasal obstruction and more annoying problems in patients. Recently, investigators have been focusing on complementary therapies alone or in conjunction with endoscopic nasal and sinus surgery. However, given the association of Vitamin D (VD) deficiency and chronic rhinosinusitis with nasal polyposis (CRSwNP) in previous studies, it may be possible to prevent the recurrence of NP and the development of rhinosinusitis by controlling serum levels of VD and maintaining it at a normal level. The current study aimed to investigate the efficacy of VD supplementation in preventing CRSwNP recurrence after endoscopic surgery. Materials and Methods: This clinical trial composed of vitamin D deficient patients with CRSwNP who were candidates for endoscopic sinus surgery in two groups of cases and controls. After endoscopic sinus surgery for all patients, we administered VD supplementation (50,000 IU) once a week for 8 weeks for cases and no further intervention for controls. The severity of symptoms was assessed using Sino-nasal outcome test (SNOT-22) and NP recurrence and recorded pre- and postintervention. Results: The findings indicated a higher mean change of SNOT-22 in the case group compared to that of the control group (36.03 ± 10.71 vs. 29.90 ± 11.99; P = 0.041). Moreover, the percentage of NP recurrence in cases was lower than controls; so that receiving VD supplementation has significantly reduced the chance of NP recurrence (odd ratio [95% confidence interval]: 0.298 [0.099–0.900]; P = 0.032). Conclusion: According to the result of the study, the administration of VD supplementation after endoscopic sinus surgery can reduce the severity of CRSwNP symptoms and NP recurrence significantly.