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To determine whether caloric intake is associated with risk of nosocomial bloodstream infection in critically ill medical patients.Prospective cohort study.Urban, academic medical intensive care unit.Patients were 138 adult patients who did not take food by mouth for ≥96 hrs after medical intensive care unit admission.Daily caloric intake was recorded for each patient. Participants subsequently were grouped into one of four categories of caloric intake: <25%, 25–49%, 50–74%, and ≥75% of average daily recommended calories based on the American College of Chest Physicians guidelines. Simplified Acute Physiology Score II and serum albumin were measured on medical intensive care unit admission. Serum glucose (average value and maximum value each day) and route of feeding (enteral, parenteral, or both) were collected daily. Nosocomial bloodstream infections were identified by infection control surveillance methods.The overall mean (±sd) daily caloric intake for all study participants was 49.4 ± 29.3% of American College of Chest Physicians guidelines. Nosocomial bloodstream infection occurred in 31 (22.4%) participants. Bivariate Cox analysis revealed that receiving ≥25% of recommended calories compared with <25% was associated with significantly lower risk of bloodstream infection (relative hazard, 0.24; 95% confidence interval, 0.10–0.60). Simplified Acute Physiology Score II also was associated with risk of nosocomial bloodstream infection (relative hazard, 1.27; 95% confidence interval, 1.01–1.60). Average daily serum glucose, admission serum albumin, time to initiating nutritional support, and route of nutrition did not affect risk of bloodstream infection. After adjustment for Simplified Acute Physiology Score II in a multivariable analysis, receiving ≥25% of recommended calories was associated with a significantly lower risk of bloodstream infection (relative hazard, 0.27; 95% confidence interval, 0.11–0.68).In the context of reducing risk of nosocomial bloodstream infections, failing to provide ≥25% of the recommended calories may be harmful. Higher caloric goals may be necessary to achieve other clinically important outcomes.