AIM:To evaluate the long-term safety of omeprazole in patients of gastroesophageal reflux disease resistant to treatment with H2 receptor antagonist.METHODS:We prospectively followed 33 patients on omeprazole therapy for severe erosive esophagitis for 5-8 years, with periodic gastrin levels, H. pyloriinfection, gastric biopsies for incidence of ECL cell hyperplasia, carcinoids, gastric atrophy and neoplasia. A total 185 patient follow-up years and 137 gastric biopsies were done.RESULTS:Among the 33 patients, 36% reached their peak gastrin levels in an average of 8 months to one year, then drifted Down slowly over 1-2 year period to just above their baseline level, 24% of the patients had a peak gastrin level above 400ng·L(-1) and one patient had a peak level above 1000ng·L(-1). One patient had a mild ECL cell hyperplasia which was self limiting and did not show any dysplastic changes. Eighteen percent of patients were positive for H. pylori infection. The gastric biopsies did not show gastric atrophy, intestinal metaplasia or neoplastic changes.CONCLUSION:In a series of 33 patients followed for 5-8 years on omeprazole therapy for severe reflux esophagitis, we did not observe any evidence of significant ECL cell hyperplasia, gastric atrophy, intestinal metaplasia, dysplasia or neoplastic changes.