Abstract: Objective To determine whether eradication of H.pylori can reverse the intestinal metaplasia (IM) to a certain extent, and how the eradication of H.pylori affects IM development by a prospective follow-up study of Helicobacter pylori-positive gastric mucosal intestinal metaplasia patients, to provide some reference for prevention of intestinal type gastric cancer and determining the best time to eradication of Helicobacter pylori. Methods A total of 280 patients who were confirmed with H.pylori infection and gastric mucosal intestinal metaplasia in the endoscopy center of the Second Affiliated Hospital of Wenzhou Medical University from April 1, 2017 to April 1, 2018 were enrolled. They were divided into two groups according to the patients' wishes and the severity and distribution of intestinal pathology, and followed up for 6 and 12 months. The differences of the pathological changes of patients with mild, moderate and severe IM in two groups were compared, respectively. Results During the follow-up of 6 months and 12 months, the degree of IM after H.pylori eradication in mild to moderate IM patients was lower than that of H.pylori patients who had not received H.pylori eradication(P<0.05). However, when it came to severe IM patients, eradicating H.pylori or not showed no significant difference in degree of IM (P>0.05). Conclusion Patients with mild or moderate IM in gastric mucosa should receive Helicobacter pylori eradication therapy as soon as H.pylori is found.It may be the best time to eradicate Helicobacter pylori.