Efforts to prevent organ failure are hampered by three barriers: (1) compartmentalization of care (ED, operating room, ICU, and so forth); (2) the difficulty of identifying early those at risk; and (3) lack of proven, effective treatments. Building on the success of the Lung Injury Prevention Study (USCIITG-LIPS),4,10 the unique, multidisciplinary, USCIIT Group network, and CTSA-funded infrastructure, USCIITG-Program for Prevention of Organ Failures (USCIITG-PROOF) will address all three barriers simultaneously through rapid-cycle, multicenter clinical trials that span clinical domains to test a variety of interventions that prevent organ failure in those at risk. USCIITG-PROOF investigators currently are working on multiple projects aimed at the prevention of acute lung injury, including LIPS-Aspirin (LIPS-A) (a National Heart, Lung, and Blood Institute-funded multicenter trial to investigate the usefulness of aspirin to prevent acute lung injury) and LIPS-B, an investigator-initiated study to examine whether budesonide and the β-agonist formoterol can prevent acute lung injury in high-risk patients. Additionally, USCIITG-PROOF will advance the methodology used to conduct clinical trials, moving away from existing manual data collection techniques toward automated extraction of clinical data from electronic medical records. The first test of this technology will come from a Centers for Medicare and Medicaid Services-sponsored, multicenter innovation award with USCIIT Group investigators and Philips Research North America. The goal of this project is to determine whether a novel acute care interface, Patient-Centered Cloud-Based Electronic System-Ambient Warning and Response Evaluation (ProCCESs AWARE), can reduce preventable errors in the ICU, improve outcomes, and reduce costs and, in the process, train > 1,400 providers to use state-of-the-art acute care informatics.11 ProCCESs AWARE aims to facilitate care in the ICU with built-in tools for best practice compliance, practice surveillance, decision support, and reporting.