Background: Several independent clinical studies have reported that Helicobacter pylori eradication therapy could achieve complete remission in some patients with H. pylori-positive early-stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: To compare the long-term results of anti-H. pylori therapy in early-stage, gastric low-grade and high-grade transformed MALT lymphoma, two multicenter prospective studies of anti-H. pylori therapy for early-stage gastric lymphoma conducted in Taiwan, one for low-grade MALT lymphoma, with 34 patients enrolled from March 1996 through April 1999, and one for high-grade transformed tumors (diffuse large B-cell lymphoma with features of MALT, DLBCL[MALT] lymphoma), with 24 patients enrolled since June 1995, were directly compared. In both studies, patients generally received 2 weeks of antibiotics and had multiple sequential follow-up endoscopic examinations until complete histologic remission (CR) or disease progression; patients were monitored through January 31, 2004. CR was defined as regression of lymphoid infiltration to Wotherspoon's score of 2 or less on all pathologic sections of endoscopic biopsy specimens. All statistical tests were two-sided. Results: The H. pylori-positive rate among the 34 low-grade patients was 94% (32 of 34). All 24 selected high-grade patients were H. pylori positive. H. pylori was eradicated in 97% (30 of 31) of evaluable H. pylori-positive low-grade patients and in 92% (22 of 24) of high-grade patients, which led to CR in 80% (24 of 30, 95% confidence interval [CI] = 65% to 95%) and 64% (14 of 22, 95% CI = 42% to 86%) of patients, respectively. None of the five patients who were either initially H. pylori negative or had persistent H. pylori infection after antibiotics achieved CR. After median follow-up of more than 5 years in complete responders, tumor recurrence was observed in three (13%) low-grade patients but not in high-grade patients. Conclusions: Anti-H. pylori therapy may be considered as one of the treatment options for early-stage H. pylori-positive gastric DLBCL(MALT), and large-scale prospective studies to validate its use as first-line therapy for such tumors should be undertaken.