Objective The purpose of this retrospective study is to evaluate the diagnostic value of contrast enhanced sonography plus gastric distention sonography, the Double Contrast-enhanced Ultrasound (DCUS) in gastric lesions. Methods 107 cases with pathology confirmed gastric lesions were retrospectively reviewed, DCUS and oral contrast agent ultrasound (US) were performed in all cases prior to operation. Perfusion parameters including arrival time (AT), peak intensity (PI), time to peak (TTP), and area under the curve (AUC) of the lesion and surrounding normal tissue were analyzed. A reader blinded to pathology results were asked to rate and compare each case with surgical or resection biopsy pathology results. Results From the 107 gastric lesions, 75 were malignant gastric lesions (33 gastric cancers, 42 gastrointestinal stromal tumors (GISTs)) and 32 were benign gastric lesions (11 inflammatory masses and 21 polypoid adenomas). Compared with US, DCUS achieved higher value in sensitivity (90.6% vs. 70.6%), specificity (75% vs. 62.5%), positive predictive value (89.5% vs. 81.5%), negative predictive value (77.4% vs. 47.6%), and overall accuracy (85.9% vs. 68.2%). When US was tested against DCUS, the increase in correct diagnoses value was significant (P=.01). Furthermore, gastric cancer had faster AT, higher PI and AUC than normal tissue (P<0.05); GIST and Inflammatory mass had higher PI than normal tissue (P<0.05); gastric cancer and GIST had faster AT than polypoid adenoma (P<0.05), Inflammatory mass showed higher PI than other 3 lesions and gastric cancer had higher PI than polypoid adenoma and GIST (P<0.05); gastric cancer and inflammatory mass had larger AUC than polypoid adenoma and GIST (P<0.05). Conclusion DCUS improved diagnostic performance compared with US. The combination of different CEUS enhancement characteristics with quantitative perfusion parameters may provide a promising tool to help differentiate gastric cancer and GIST from benign lesions.