BACKGROUND/AIMS: We performed this prospective study to evaluate the long-term outcome of patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma after H. pylori eradication. We also investigated the relationship between p16 hypermethylation and the remission of MALT lymphoma in the patients. METHODS: We prospectively enrolled 21 patients with H. pylori-positive low-grade gastric MALT lymphoma (stage IE1). The patients received the eradication therapy of H. pylori and then, follow-up endoscopic and histologic examinations were performed at regular intervals. Methylation-specific polymerase chain reaction (MSP) method was used for the serial detection of p16 hypermethylation. RESULTS: Nineteen patients (90.5%) achieved complete remission and their median duration of remission was 15.7 months. One patient had a relapse of MALT lymphoma for two times. Seven patients (58%) revealed p16 hypermethylation initially and in 3 patients who were followed-up for median 28 months, p16 hypermethylation was disappeared. CONCLUSIONS: Complete remission of low-grade gastric MALT lymphoma after H. pylori eradication could be maintained in long-term period. Further studies are needed to investigate a role of p16 hypermethylation in the pathogenesis of gastric MALT lymphoma.