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Postoperative hospital-acquired infections (HAIs) may result from disruption of natural barrier sites. Recent studies have linked vitamin D status and barrier site integrity.To investigate the association between preoperative vitamin D status and the risk for HAIs.A retrospective analysis was performed using propensity score methods to construct a matched-pairs cohort to reduce baseline differences between patients with 25-hydroxyvitamin D (25[OH]D) levels less than 30 ng/mL vs 30 ng/mL or greater. Multivariable logistic regression analysis was then performed to examine the association between 25(OH)D levels and HAIs while adjusting for additional perioperative factors. Locally weighted scatterplot smoothing was used to depict the relationship between increasing 25(OH)D levels and the risk for HAIs. This study was conducted in a single, teaching hospital in Boston, Massachusetts, and involved 770 gastric bypass surgery patients between January 1, 2007, and December 31, 2011.Preoperative 25(OH)D levels.Association between preoperative 25(OH)D levels and the risk for postoperative HAIs.The risk for HAIs was 3-fold greater (adjusted odds ratio, 3.05; 95% CI, 1.34-6.94) in patients with 25(OH)D levels less than 30 ng/mL vs 30 ng/mL or greater. Further adjustment for additional perioperative factors did not materially change this association. Locally weighted scatterplot smoothing analysis depicted a near inverse linear relationship between vitamin D status and the risk for HAIs for 25(OH)D levels around 30 ng/mL.In our patient cohort, a significant inverse association was observed between preoperative 25(OH)D levels and the risk for HAIs. These results suggest that preoperative 25(OH)D levels may be a modifiable risk factor for postoperative nosocomial infections. Prospective studies must determine whether there is a potential benefit to preoperative optimization of vitamin D status.