Programs to reduce central line-associated bloodstream infections (CLABSIs) have improved the safety of hospitalized patients. Efforts are underway to disseminate these successes broadly to reduce other types of hospital-acquired infectious and noninfectious preventable harms. Unfortunately, the ability to broadly measure and prevent other types of preventable harms, especially infectious harms, needs enhancement. Moreover, an overarching research framework for creating and integrating evidence will help expedite the development of national prevention programs. This article outlines a 5-phase translational (T) framework to develop robust research programs that reduce preventable harm, as follows: phase T0, discover opportunities and approaches to prevent adverse health care events; phase T1, use T0 discoveries to develop and test interventions on a small scale; phase T2, broaden and strengthen the evidence base for promising interventions to develop evidence-based guidelines; phase T3, translate guidelines into clinical practice; and phase T4, implement and evaluate T3 work on a national and international scale. Policy makers should use this framework to fill in the knowledge gaps, coordinate efforts among federal agencies, and prioritize research funding.