As chronic use of antiulcer medications might predispose older persons to cobalamin deficiency, we studied participants (> 65 years) in the clinical examination of the Canadian Study of Health and Aging to test the association between the use of an antiulcer medication (histamine-2 blocker or proton pump inhibitor) at baseline with initiation of cobalamin replacement during the 5 year follow-up period. Of 1054 eligible subjects, 125 (11.7%) were taking an antiulcer medication at baseline. At follow-up, 49 (4.6%) had started cobalamin replacement. Antiulcer medication use at baseline was significantly associated with the initiation of cobalamin therapy (odds ratio 2.56, 95% confidence interval 1.30-5.05), even after adjusting for age, gender and institutional residence (odds ratio 2.61, 95% confidence interval 1.31-5.23). There is an independent association between the use of antiulcer medication and initiation of cobalamin therapy. While the relationship is not unambiguously causal, this finding underscores the need for judicious prescribing of antiulcer medications for older persons.