BACKGROUND & AIMS: Eradication of Helicobacter pylori infections in humans results in the healing of gastritis and gastric ulcers. This study used a mouse model to test whether oral vaccination can cure Helicobacter infection and gastritis. METHODS: Mice were infected with Helicobacter felis. Three weeks after infection, the mice were orally immunized with H. pylori urease B subunit. Control mice were simultaneously infected but sham immunized. RESULTS: Three to 8 weeks after oral immunization of H. felis-infected mice with recombinant H. pylori urease B subunit, the infection cleared and there was no evidence of gastritis. Vaccinated mice remained protected against two consecutive H. felis challenges. CONCLUSIONS: These results show that the lack of natural immunity against Helicobacter can be overcome by oral immunization and that vaccination offers a novel therapeutic approach to Helicobacter-induced gastritis.