The number of handoffs a patient experiences while hospitalized has almost certainly increased at academic institutions after the implementation of duty hour restrictions, posing a significant threat to patient safety. In response, The Joint Commission required that all hospitals maintain a standardized approach to handoff communication, and in 2010 the Accreditation Council for Graduate Medical Education required that all residents receive formal handoff training. This multicenter study demonstrates that implementation of a standardized handoff bundle—which included a mnemonic ("I-PASS") for standardized oral and written signouts, formal training in handoff communication, faculty development, and efforts to ensure sustainability—was associated with a 23% relative reduction in the incidence of preventable adverse events across 9 participating pediatric residency programs. This improvement was achieved through a very high level of resident engagement in the revised handoff process, but did not negatively affect resident workflow. This rigorously designed and analyzed study establishes the I-PASS model as the gold standard for effective clinical handoffs and demonstrates the value of methodologically stringent approaches to addressing patient safety issues. A case of a delayed diagnosis due to poor handoffs is discussed in a past AHRQ WebM&M commentary.