BACKGROUND:Identifying patients most at risk for hospital-and community-associated infections is one essential strategy for preventing infections. OBJECTIVE: To investigate whether rates of community-and healthcare-associated bloodstream and surgical site infections varied by patient gender in a large cohort after controlling for a wide variety of possible confounders. DESIGN: Retrospective cohort study. PARTICIPANTS: All patients discharged from January 1, 2006 through December 31, 2008 (133,756 adult discharges and 66,592 pediatric discharges) from a 650-bed tertiary care hospital, a 220-bed community hospital, and a 280-bed pediatric acute care hospital within a large, academic medical center in New York, NY. MAIN MEASURES: Data were collected retrospectively from various electronic sources shared by the hospitals and linked using patients' unique medical record numbers. Infections were identified using previously validated computerized algorithms. KEY RESULTS: Odds of community-associated bloodstream infections, healthcare-associated bloodstream infections, and surgical site infections were significantly lower for women than for men after controlling for present-on-admission patient characteristics and events during the hospital stay [odds ratios (95 % confidence intervals) were 0. 85 (0.77-0.93), 0.82 (0.74-0.91), and 0.78 (0.68-0.91), respectively]. Gender differences were greatest for older adolescents (12-17 years) and adults 18-49 years and least for young children (<12 years) and older adults (≥70 years). CONCLUSIONS: In this cohort, men were at higher risk for bloodstream and surgical site infections, possibly due to differences in propensity for skin colonization or other anatomical differences.