OBJECTIVE: To examine the effects of a mechanical ventilation weaning management protocol that was implemented as a hospital-wide, quality improvement program on clinical and economic outcomes. DESIGN: Prospective, before-and-after intervention study. Data from a preimplementation year are compared with those of the first 2 yrs after protocol implementation. PATIENTS AND SETTING: Patients older than 18 yrs in diagnosis-related group 475 and group 483, who were admitted to the adult medical, surgical, and cardiac intensive care units (ICU) in a university hospital. INTERVENTIONS: After the baseline year, a weaning management program was implemented throughout our institution. Primary endpoints were mortality, days on mechanical ventilation, ICU and hospital lengths of stay, hospital costs, and the percentage of patients requiring tracheostomy. MAIN RESULTS: The number of patients increased from 220 in the baseline year (year 0) to 247 in the first year (year 1), then to 267 in the second year (year 2). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score increased from 22.2 to 24.4 in year 1 (p =.006) and to 26.2 in year 2 (p CONCLUSIONS: A multifaceted, multidisciplinary weaning management program can change the process of care used for weaning patients from mechanical ventilation throughout an acute care hospital and across multiple services. This change can lead to large reductions in the duration of mechanical ventilation, length of stay, and hospital costs, even at a time when patients are sicker.