Abstract Introduction Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy, uncontrolled use of these agents may select for more-resistant organisms. This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia. Methods We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation (DE) with conventional antimicrobial treatment (non-de-escalation, NDE) in critically ill patients with hospital-acquired pneumonia (HAP). This open-label, randomized clinical trial was performed in patients in a tertiary-care center medical intensive care unit (MICU) in Korea. Patients ( n = 54) randomized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results, whereas patients randomized to the NDE group ( n = 55) received noncarbapenem, nonvancomycin empiric antimicrobials. Results Between November 2004 and October 2006, 109 MICU patients with HAP were enrolled. Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms (100% versus 14.3%; P