Objective To study the diagnostic efficiency of Gastroesophageal Reflux Disease (GRED) with mix liquid of oral ultrasound microbubble SonoVue and gastroenterologic ultrasound developer.Methods The clinical diagnosis of 66 GRED patients were collected from May 2018 to November 2019 in our hospital, including 31 male and 35 female cases, aged from 21 to 82, with an average age of （515±1424). A retrospective analysis of the 66 GRED patients was conducted by comparing the diagnosis results of gastroenterultrasound developer (Stomach Ultrasound Developer Group) with mix liquid of oral ultrasound microbubble SonoVue and Stomach ultrasound developer (Mixture Group). Oral ultrasound microbubble SonoVue and gastroenterultrasound developer were mixed by 2.5∶500. The sonogram features of GRED were observed in convential mode and angiographic mode respectively. The frequency spectrum Doppler was used to record the reflux time, reflux frequency and reflux speed and the diagnostic efficacy of stomach ultrasound Developer Group and Mix Liquid Group were compared. The results were compared with gastroscopy and all 66 cases were collected by detection results of gastroscopy and gastroscope specimen. Results 53 cases were detected by Mixture Group with positive rate 803% (53/66), 13 cases were not detected with negative rate 19.7%. 42 cases were detected by stomach ultrasound Developer Group with positive rate 6364%(42/66), 24 cases were not detected with negative rate 3636%. 21 cases were detected by gastroscopy with positive rate 3182%(21/66), 45 cases were not detectedwith negative rate 6818%. The diagnostic efficacy of the mixture group was significantly higher than that of the stomach ultrasound developer (P＜0.05), as well as the gastroscope group (P＜0.05). There were 11 esophageal hiatal hernia cases in 53 GRED patients. Conclusion Oral SonoVue microbubble contrast agent and gastric adjuvant mixture is superior to single gastric adjuvant and gastroscope in the diagnosis of GERD in contrast-enhanced ultrasound mode. It can show whether there is reflux image, reflux width and reflux height in real-time and objectively. It can significantly improve the diagnostic efficiency of GERD and open up a new inspection method for clinical diagnosis of GERD.