Recent studies suggest that intranasally administered vitamin D can be an effective treatment for patients with chronic rhinosinusitis (CRS). We performed a double-blind, placebo-controlled, randomized clinical trial to evaluate the effect of adding calcifediol to saline sinus irrigation with budesonide for patients with CRS.A total of 113 adult patients with CRS were enrolled. Patients were randomized to either calcifediol (n = 58, 51%) or placebo (n = 55, 49%) lavage and were instructed to irrigate both nasal cavities twice daily for 21 days, with either calcifediol or placebo dissolved in a solution of saline with budesonide. The primary outcome measure was the change in Sino-Nasal Outcome Test (SNOT-22) scores, endoscopic examination scored by the Lund-Kennedy (L-K) grading system, and physician-reported response to treatment, as measured with decreased need for nasal steroids/cessation of nasal steroids in the calcifediol group compared with the placebo group. The secondary outcome measures included the change in serum 25(OH)D concentration and the correlation of results with other clinical data.108 patients completed the trial. Significant changes in SNOT-22 score, L-K score and serum 25(OH)D were reported between the 2 study groups. A significant percentage of participants in the calcifediol group could cease nasal steroids.Calcifediol in saline nasal lavage with budesonide results in clinically significant benefits beyond the benefits of saline with budesonide alone for patients with CRS.