The relationships between Hp infection and NUD are uncertain. Consequently, the clinical benefit of the eradication remains controversial. The aim of this multicenter, randomized, double-blind, placebo-controlled study was to determine the effect of Hp eradication on symptoms of dyspepsia 12 months after treatment. Methods: 253 patients with severe ulcer-like pain (grade 3 or 4 on Likert scale: from 0= none to 4= very severe) for at least 3 months, Hp infection (Clo-Testregistered with histological confirmation) and no evidence of peptic ulcer or esophagitis on upper GI endoscopy were treated. Patients were randomly allocated to a 7-day treatment of ranitidine 3OOmgx2, amoxicilline Igx2, clarithromycine 5OOmgx2 (RAe) or placebo (PLA) and were followed-up for 12 months (day 8 and months 3, 6, 9 and 12). Treatment success was defined as the reduction of at least 2 grades on Likert scale between randomization and the 12-month visit. Complete resolution of dyspeptic symptoms was defined as grade 0 on Likert scale. Presence of Hp was assessed at 3 months by l3C-urea breath-test and at 12 months by histology. Gastritis was histologically graded (Sydney System) on 2 antral and 2 corpus biopsies performed at randomization and at 12 months by an expert gastrointestinal pathologist blinded to treatment group. Results: The 2 groups were comparable. Hp eradication rates at 3 months were 70% in RAC and 9% in PLA group, and at 12 months 69% and 18% respectively. By intention to treat there was no significant difference at 12 months between the 2 groups in treatment success rates (62% RAC and 60% PLA). However, complete symptom resolution was significantly more frequent (p<0.05) in RAC group (43%) than in PLA group (31%). In RAC group, treatment success rates were 84% among patients with Hp eradication and 64% among patients with persistent infection at 12 months (p=O.04). Chronic gastritis persisted in 91% of patients in RAC group and 89% of patients in PLA group after 12 months. However, histological scores for inflammation, activity and lymphoid infiltration were significantly higher in PLA group than in RAC group. Scores for atrophy and metaplasia were similar in the 2 groups. Conclusion: Curing Hp infection in NUD patients is more likely associated with complete symptom relief at 12 months despite the large placebo effect in reducing dyspeptic symptoms severity. Moreover, chronic gastritis persisted with improvement of inflammation and activity 1 year after Hp eradication treatment.