Context Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infec tions (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. Objective To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. Design, Setting, and Participants Randomized, double-blind, placebo- controlled trial conducted among 322 healthy adults between February 2010 and No- vember 2011 in Christchurch, New Zealand. Intervention Participants were randomly assigned to receive an initial dose of 200 000 IU oral vitamin D3, then 200 000 IU 1 month later, then 100 000 IU monthly (n=161), or placebo administered in an identical dosing regimen (n=161), for a total of 18 months. Main Outcome Measures The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. Results The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vi- tamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/ml throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by sea- son and by baseline 25-OHD levels. Conclusion In this trial, monthly administration of 100 000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults