Our objective was to determine prescribing patterns for H2 receptor antagonists (H2RA) in primary care and to establish the prevalence and impact of Helicobacter pylori (Hp) eradication in this population of patients. Patients on long-term (6 months or longer) H2RA were identified through a computerized database at the six primary care practices in North England. Hp status was identified by serology, and those positive received standard proton pump-based triple therapy followed by a urea breath test to confirm Hp eradication. The main outcome measures were the indications for prescribing long-term H2RA in primary care, the prevalence of patients with a positive Hp serology, and the impact of Hp eradication on the subsequent need for acid suppression, severity of dyspepsia, gastrointestinal symptom rating score (GSRS), quality of life (QOL), and overall feeling of well-being. One thousand seven (1.5%) patients were on long-term H2RA. Peptic ulcer disease (PUD) was the most common indication for prescribing (42%), followed by nonulcer dyspepsia (28%) and gastroesophageal reflux disease (23%). In 81% of the patients treatment with H2RA therapy followed a previous endoscopic or radiological investigation. Only 27 (2.5%) patients had had their Hp status checked within the last 6 months. Of the 471 patients who eventually had their Hp serology tested, 297 (63%) were Hp positive. Fifty-eight percent of the Hp-positive patients had PUD. Successful Hp eradication was achieved in 250 (84%) of the patients, of whom 247 (83%) finished the 1-year follow-up. This was associated with a significant reduction in the amount of H2RA being consumed (P < 0.00001). There was also a significant improvement in the symptom scores and the GSRS after successful Hp eradication (P < 0.00001). Overall 67% of the patients reported an improvement in the QOL and 77% noted a feeling of well-being 1 year after Hp eradication. A significant proportion of patients in primary care is still being maintained on long-term H2RA, imposing a considerable financial drain on the NHS resources. Approximately two-thirds of these patients will be Hp positive, and among them the largest group will comprise patients with PUD. Hp eradication in such patients results in a significant reduction in usage of acid suppression and an improvement in overall QOL and severity of dyspeptic symptoms.