Patients requiring intensive care are particularly vulnerable to preventable adverse events, including health care–associated infections. This AHRQ-funded study examined the effect of a collaborative to prevent adverse events in patients requiring mechanical ventilation in 56 intensive care units (ICUs) in 2 states over a 3-year period. The participating ICUs introduced a multifaceted intervention structured around the Comprehensive Unit-based Safety Program, focusing on implementing evidence-based safety processes by explicitly addressing barriers to improvement and engaging in regular data audit and feedback. Participating hospitals were able to significantly reduce the rate of ventilator-associated adverse events (including ventilator-associated pneumonia) over the study period. Although the study is limited by lack of a concurrent control group, the results indicate the power of collaborative efforts to drive large-scale improvement.