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Bedside lung ultrasound (LUS) is useful in detecting radio-occult pleural-pulmonary lesions. The aim of our study is to compare the value of LUS with other conventional routine diagnostic tools in the emergency department (ED) evaluation of patients with pleuritic pain and silent chest radiography (CXR).Ninety patients consecutively admitted to the ED with pleuritic pain and normal CXR were retrospectively (n = 49) and prospectively (n = 41) studied. All patients were blindly examined by LUS and submitted to clinical examination and blood samples. The ability of blood tests and symptoms to predict any radio-occult pleural-pulmonary condition confirmed by conclusive image techniques and follow-up was evaluated and compared with LUS.In 57 cases, the final diagnosis was chest wall pain. The other 33 patients were diagnosed with a pleural-pulmonary condition (22 pneumonia, 2 pleuritis, 7 pulmonary embolism, 1 lung cancer, 1 pneumothorax). Lung ultrasound showed a sensitivity of 96.97% (95% confidence interval [CI], 84.68%-99.46%) and a specificity of 96.49% (95% CI, 88.08%-99.03%) in predicting radio-occult pleural-pulmonary lesions and significantly higher area under the curve (AUC) of receiver operating characteristic analysis (AUC, 0.967; 95% CI, 0.929–1.00) than d-dimer (AUC, 0.815; 95% CI, 0.720–0.911) and white blood cell count (AUC, 0.778; 95% CI, 0.678–0.858). None of the other routine tests considered or a combination between them better predicted the final diagnosis.Chest radiography and blood tests may be inadequate in the diagnostic process of pleuritic pain. In case of silent CXR, LUS is critical for identifying patients with pleural-pulmonary radio-occult conditions at bedside and cannot be safely replaced by other conventional methods.