Objective The aim of this study was to assess the diagnostic accuracy of lung ultrasonography (LUS) for high-altitude pulmonary edema (HAPE). Background LUS has proven to be a reliable tool for the diagnosis of pulmonary diseases, including pneumonia, acute respiratory distress syndrome (ARDS), and pneumothorax. LUS also has potential for the diagnosis of HAPE. However, the actual diagnostic value of LUS for HAPE is still unknown. Our objective was to determine the feasibility of using LUS for the diagnosis of HAPE. Materials and Methods A prospective clinical research study of adult HAPE patients was conducted. LUS and chest X-ray (CXR) were performed in patients with suspected HAPE before and after treatment, and pulmonary moist rales were recorded concurrently. The diagnostic value of LUS, CXR, and moist rales for HAPE (i.e., their sensitivity, specificity, and positive and negative predictive values) were assessed, and the results were compared. The gold standard was the final diagnosis. Results In total, 148 patients were enrolled in the study, 126 of which were diagnosed with HAPE (85.14%). Before treatment, the diagnostic accuracy of LUS for HAPE was as follows: sensitivity, 98.41% (95% confidence interval (CI) 100.60–96.23%); specificity, 90.91% (95% CI 102.92–78.90%). LUS had higher sensitivity (0.98 vs. 0.81, P < 0.01 using the McNemar test) than moist rales for the diagnosis of HAPE. LUS also had higher sensitivity than CXR (0.98 vs. 0.93, P < 0.05 using the McNemar test). After treatment, LUS was consistent with CXR in 96.55% of HAPE patients, and the concordance between LUS and CXR was high (k statistic = 0.483 P ≤ 0.001; 95% CI −0.021 to −0.853). Conclusion The results indicate that LUS is a reliable method for the diagnosis and surveillance of HAPE. This trial is registered with Chinese Clinical Trial Registry (No. ChiCTR-DDD-16009841).