OBJECTIVES: To determine if the use of a protocol and special order form for the sedation of mechanically ventilated patients reduced the incidence of adverse clinical outcomes and reduced the cost of care of those patients. METHODS: In 2003 the hospital's costs of propofol, an intravenous sedation agent had increased by fivefold over 2002. In addition, the frequency of ventilator-associated pneumonias ("VAP"), and average duration of time for ventilation, both increased throughout 2003. An evidence-based protocol was developed, requiring certain conditions to be met before propofol could be used, and was implemented in January, 2004. In June, 2004, the pharmacy and nursing departments worked together with key physicians to ensure the protocol was being followed and appropriate selections were made from available alternatives. The length of stay in the ICU, during of ventilation, frequency of VAP, and dollars expended on intravenous sedation agents were compared between three periods: 2003 (pre-protocol), the first five-months of 2004 (protocol in place but not enforced), and the second five-months of 2004, in which the protocol was enforced by pharmacy and nursing. RESULTS: All measured parameters and outcomes in the second five month period showed a statistically significant improvement over both 2003 and the first five-months of 2004. Compliance with the protocol improved significantly between the first and second five month periods in 2004. There was no statistical difference in outcomes between 2003 and the first protocol period. CONCLUSION: The use of a sedation protocol should be successful at reducing costs of propofol and reducing the negative clinical aspects associated with mechanical ventilation. The use of a protocol built on evidence based medicine is a good first step towards improving clinical and economic outcomes; however, it must be accompanied by physician education and enforcement, and a collaboration between physicians, nursing, and pharmacy.