Health care-associated infections affect an estimated 5% of hospitalized patients and represent one of the leading causes of illness and death in the United States. This study calculates the costs and benefits of a patient safety program in intensive care units in 6 hospitals that were part of the Michigan Keystone ICU Patient Safety Program. On average, 29.9 catheter-related bloodstream infections and 18.0 cases of ventilator-associated pneumonia were averted per hospital on an annual basis. The average cost of the intervention is $3375 per infection averted, measured in 2007 dollars. The cost of the intervention is substantially less than estimates of the additional health care costs associated with these infections, which range from $12 208 to $56 167 per infection episode. These results do not take into account the additional effect of the Michigan Keystone program in terms of reducing cases of sepsis or its effects in terms of preventing mortality, improving teamwork, and reducing nurse turnover.