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OBJECTIVE:: Adjusted costs of mechanical ventilation (MV) are $1,500 per patient-day. We compared the prevalence, characteristics, and outcomes of MV <96 hrs (MV<96) and prolonged acute MV (PAMV) of >/=96 hrs' duration in a representative sample of U.S. hospital discharges. DESIGN:: A multicenter cross-sectional study. SETTING:: Nationally representative sample of U.S. hospital discharges. PATIENTS:: Adult hospital discharges were identified from the 2003 Nationwide Inpatient Sample, Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality (AHRQ). PAMV was based on the presence of ICD-9 code 96.72, and MV <96 hrs based on ICD-9 codes 96.70 and 96.71. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Of 31,340,578 discharges for adults (>/=18 yrs), 2.4% had any MV, of which 469,168 (61%) had MV<96, and 294,333 (39%) had PAMV. Patient demographics were similar for MV<96 and PAMV. With the exception of acute myocardial infarction and chronic and end-stage renal disease without dialysis, the prevalence of coexisting conditions was higher in the PAMV group. Median length of stay (17 vs. 6 days) and hospital costs ($40,903 vs. $13,434) also were higher with PAMV vs. MV<96. Although Agency for Healthcare Research and Quality disease severity and mortality probability were higher in the PAMV than MV<96 group, actual mortality was similar between the two groups (34% vs. 35%). CONCLUSIONS:: There were nearly 300,000 PAMV discharges in the United States in 2003 at an annual aggregated hospital cost of >$16 billion, or nearly two thirds of the cost for all of the MV discharges. Despite a higher predicted mortality, patients requiring PAMV had the same likelihood of being discharged alive as those on shorter-term MV. These analyses will help inform health care decision-making and resource planning in the face of an aging population. [ABSTRACT FROM AUTHOR]