Hypothesis: Allowing adequate time for laboratory and culture results before initial treatment may be associated with a worse outcome in nosocomial infections. Design: Cohort study of all episodes of nosocomial infection from December 10, 1996, to October 28, 1998. Setting: Surgical services at a university hospital. Patients and Methods: In surgical patients presenting with fever, 372 episodes of nosocomial infection were evaluated. Nosocomial infections were divided by time from fever to intervention (≤12, 13-24, and > 24 hours). These groups were subdivided by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores into low (≤10 [n = 114]), moderate (11-20 [n = 169]), and high severity of illness (>20 [n = 89]). Pneumonia and blood stream infections were divided by APACHE II scores into low (≤15 [n = 55 and n = 56, respectively]) or high severity of illness (> 15 [n = 84 and n = 77, respectively]). Main Outcome Measures: Mortality, length of stay. Results: No difference in outcome was seen between different time intervals from fever to intervention for nosocomial infections in patients with APACHE II scores of no more than 10. Patients treated more than 24 hours after fever were significantly younger than those treated at no more than 12 and 13 to 24 hours with APACHE II scores of 11 to 20 (P<.05) and more than 20 (P<.05). Mortality and length of stay for patients treated at later time intervals were comparable with those of patients treated earlier with similar APACHE II scores. There was no difference in outcome for patients with pneumonia or bloodstream infection. Conclusions: Episodes of infection in which treatment was withheld until initial microbiologic data were available (24 hours) did not have worse outcomes compared with those treated earlier. Waiting for laboratory and culture results to direct antibiotic therapy for nosocomial infections does not appear harmful and may be potentially beneficial.