Patients with hereditary diffuse gastric cancer (HDGC) and germline mutations in the E-cadherin gene, , have a very high cumulative lifetime risk of developing diffuse gastric cancer. In these patients, it is formally recommended to perform a prophylactic total gastrectomy (PTG). We analyzed the course of patients with HDGC who have undergone PTG in our institution. Pedigree analysis, preoperative screening results, operative course, postoperative data, and complete stomach pathologic examination were performed in all patients. Seven patients with confirmed mutation underwent PTG, five were women, and average age was 27 years (range 17-42). Signet ring cell carcinoma was found in 1 patient in the preoperative surveillance endoscopic biopsies. Laparoscopic PTG was performed in all patients. There were two complications, an intestinal obstruction that required reintervention and an asymptomatic esophagojejunal anastomosis leak that resolved with conservative treatment. In all gastrectomy specimens, intramucosal signet ring cell carcinoma foci limited to the lamina propria were found (range 1-31), 83.5% were in the body-fundus region. The mean follow-up was 28.5 months (range 8-72). The mean weight loss was 9% (range 2-18). Postoperative symptoms associated with Dumping syndrome were the most frequent. All the patients reported of being very satisfied with the procedure and of having a better quality of life than expected before the procedure. Laparoscopic PTG is an excellent resource to prevent the development of advanced diffuse gastric cancer (DGC) in patients with HDGC with mutation. The procedure was well tolerated with a high satisfaction rate and very good functional results. It should be considered in these patients due to the high risk of developing advanced DGC and the lack of effective and reliable surveillance studies.