Rationale: Health care associated bloodstream infections are common in critically ill patients; however, investigators have had difficulty in quantifying the clinical impact of these infections given the high-expected mortality among these patients. Objective: To estimate the impact of health care associated bloodstream infections on in-hospital mortality after adjusting for severity of illness at critical care admission. Method: A cohort of medical and surgical intensive care unit patients. Measurements: Severity of illness at admission, bloodstream infection, and inhospital mortality. Main Results: Among the 2,783 adult patients, 269 developed unit associated bloodstream infections. After adjusting for severity of illness, patients with a lower initial severity of illness who developed an infection had a greater than two-fold higher risk for in-hospital mortality (HR= 2.42, 95%CI (1.70, 3.44), p<0.01) when compared to patients without infection and with a similar initial severity of illness. In contrast, patients with a higher initial severity of illness who subsequently developed an infection did not have an increased risk for inhospital mortality (HR=0.96, 95%CI 0.76, 1.23) when compared to patients without infection but with a similar initial severity of illness. Conclusions: These results suggest that these infections in less ill patients have a higher attributable impact on subsequent mortality than in more severely ill patients. Focusing interventions to prevent bloodstream infections in less severely ill patients would be expected to have a greater benefit in terms of mortality reduction.