OBJECTIVE Chest radiography (chest x-ray [CXR] and chest computed tomography [CT]) is the most common imaging in blunt trauma evaluation. Unnecessary trauma imaging leads to greater costs, emergency department time, and patient exposure to ionizing radiation. OBJECTIVE To validate our previously derived decision instrument (NEXUS Chest) for identification of blunt trauma patients with very low risk of thoracic injury seen on chest imaging (TICI). We hypothesized that NEXUS Chest would have high sensitivity (>98%) for the prediction of TICI and TICI with major clinical significance. METHODS From December 2009 to January 2012, we enrolled blunt trauma patients older than 14 years who received chest radiography in this prospective, observational, diagnostic decision instrument study at 9 US level I trauma centers. Prior to viewing radiographic results, physicians recorded the presence or absence of the NEXUS Chest 7 clinical criteria (age >60 years, rapid deceleration mechanism, chest pain, intoxication, abnormal alertness/mental status, distracting painful injury, and tenderness to chest wall palpation). METHODS Thoracic injury seen on chest imaging was defined as pneumothorax, hemothorax, aortic or great vessel injury, 2 or more rib fractures, ruptured diaphragm, sternal fracture, and pulmonary contusion or laceration seen on radiographs. An expert panel generated an a priori classification of clinically major, minor, and insignificant TICIs according to associated management changes. RESULTS Of 9905 enrolled patients, 43.1% had a single CXR, 42.0% had CXR and chest CT, 6.7% had CXR and abdominal CT (without chest CT), 5.5% had multiple CXRs without CT, and 2.6% had chest CT alone in the emergency department. The most common trauma mechanisms were motorized vehicle crash (43.9%), fall (27.5%), pedestrian struck by motorized vehicle (10.7%), bicycle crash (6.3%), and struck by blunt object, fists, or kicked (5.8%). Thoracic injury seen on chest imaging was seen in 1478 (14.9%) patients with 363 (24.6%) of these having major clinical significance, 1079 (73.0%) minor clinical significance, and 36 (2.4%) no clinical significance. NEXUS Chest had a sensitivity of 98.8% (95% CI, 98.1%-99.3%), a negative predictive value of 98.5% (95% CI, 97.6%.6-99.1%), and a specificity of 13.3% (95% CI, 12.6%-14.1%) for TICI. The sensitivity and negative predictive value for TICI with clinically major injury were 99.7% (95% CI, 98.2%-100.0%) and 99.9% (95% CI, 99.4%-100.0%), respectively. CONCLUSIONS We have validated the NEXUS Chest decision instrument, which may safely reduce the need for chest imaging in blunt trauma patients older than 14 years.