The first case of cobalamin deficiency with megaloblastic anaemia in a patient under long-term omeprazole therapy is presented. This patient received omeprazole at a daily dose of 40–60 mg for 4 years as treatment for a gastro-oesophagal reflux complicated by peptic oesophagitis. Seric vitamin B12 was dramatically decreased at 80 pmol L-1. The Schilling test was normal (13%) with crystalline [57Co] cobalamin and it was at 0% with [57Co] cobalamin-labelled trout meat. All other assimilation tests were normal except an expiratory hydrogen breath test performed with lactulose. The haematological status was restored after intramuscular treatment with cobalamin. In conclusion, prolonged omeprazole therapy can be responsible for a cobalamin deficiency due to protein-bound cobalamin malabsorption.