Pediatric inpatients are at high risk for adverse drug events (ADEs). Pediatric-specific trigger tools and computerized surveillance systems are effective methods to detect ADEs and identify opportunities for prevention. This performance-improvement collaborative implemented a multifaceted change strategy in 13 institutions and produced a 42% reduction in ADEs. The change strategies included efforts to reduce interruptions during medication administration, adopt consensus-based protocols and order sets, ensure high reliability with the Five Rights, and foster a culture of safety. The interventions had the greatest impact on opioid-related ADEs, which decreased by 51% across participating hospitals. The authors recommend using quality improvement collaboratives to drive improved patient care.