Helicobacter pylori (HP) infection is the most important cause of non-cardia gastric cancer, which is triggered by chronic gastric inflammation. Eradication of HP could reduce the risk of subsequent gastric cancer by about 50%, but not totally eliminate the risk. In particular, patients with advanced pre-neoplastic gastric lesions may still progress to gastric cancer development despite successful HP eradication. In this regard, we have recently shown that eradication in older patients (>60 years) could still result in significant reduction in gastric cancer risk [1]. The chemopreventive effects, however, would be more obvious with longer time lapse (>10 years) from eradication therapy. Apart from HP eradication, we have also evaluated the roles of other potential chemopreventive agents on post-HP eradication gastric cancer development. Aspirin is one of the most frequently used chemopreventive agents, particularly on prevention of gastrointestinal cancers. Our territory wide cohort study showed that the use of aspirin was associated with a frequency-, dose-, and duration-dependent reduction in gastric cancer risk after HP eradication [2]. The effect was most prominent in those who used aspirin daily or for five or more years. Moreover, the use of metformin was also found to reduce the risk of gastric cancer development among diabetic patients who had HP eradicated [3]. In contrast, gastric atrophy is generally considered to be an important risk factor for gastric cancer. It however remains controversial whether the use of proton pump inhibitors (PPIs), with potent acid suppressive effects, would result in a higher risk of gastric cancer. Past studies are largely confounded by the difference in HP infection statuses and relatively short follow up duration. Our recent study showed that even after H. pylori eradication, long term use of PPIs are still associated with an increased risk of gastric cancer by about two-fold [4]. Subgroup analysis further showed that the increased cancer risk was only observed among those non-aspirin users but not aspirin users. Hence, long-term PPIs could still be used cautiously among high risk patients. In conclusion, we have shown in this series of studies that chemopreventive agents (aspirin and metformin) as well PPIs could further modulate the risk of gastric cancer development after HP eradication.