Lower extremity deep vein thrombosis (DVT) is a frequent cause of admission to the emergency departments (ED). Although the gold standard for diagnosis is the Duplex ultrasound examination, the current study used for diagnosis of DVT in the ED by emergency physicians is the point-of-care compression ultrasound (POCUS). To compare the sensitivity and specificity of the two-point and three-point compression ultrasound (2PCUS and 3PCUS respectively) for diagnosis of lower extremity DVT in an ED management. We prospectively recruited outpatients who were admitted to the ED with suspected lower extremity DVT. Each patient underwent 2PCUS and 3PCUS performed by a trained ED physician. The ED physician recorded the results and then referred the patient to the vascular clinic for the Duplex ultrasound examination. 195 patients recruited to this study between July 2015 and June 2016 in the ED of Rabin Medical Center-Beillinson Hospital, Israel. DVT was diagnosed by Duplex examination in 48 of 195 patients (24.6%). There were significant correlations among the findings regarding the deep veins on both the 2PCUS and 3PCUS tests and on the Duplex examination (p < 0.001). DVT at any vein was correctly diagnosed with the 2PCUS in 38 of48 patients with positive findings on Duplex examination and incorrectly diagnosed (false positive) in 2 of 133 patients without DVT (sensitivity 82.76%, specificity 98.52%). DVT was correctly diagnosed with the 3PCUS in 43 of 48 DVT and incorrectly diagnosed (false positive) in 2 of133 patients without DVT (sensitivity 90.57%, specificity 98.52%). The sensitivity of the 3PCUS was significantly higher than the 2PCUS (p < 0.001), while the specificity was similar. A short training is satisfactory for achieving a good clinical capability to identify DVT by ED physicians. The 3PCUS examination preformed in the ED, is a noninvasive, accurate and quick diagnostic test for evaluation of patients presenting with signs and symptoms suggestive of a DVT. By Using 3PCUS, the ED physicians may decrease time to diagnosis, definitive care and length of stay in the ED.