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Crohn's disease (CD) can commonly involve the terminal ileum, which is the site of B12 absorption. The aim of this study was to define the prevalence of vitamin B12 abnormalities in a population with CD and to identify risk factors associated with B12 abnormalities in CD.The medical records of 201 patients with CD evaluated at a tertiary care center were retrospectively reviewed to determine the prevalence of B12 deficiency and to evaluate factors associated with B12 deficiency. The prevalence of B12 deficiency in a control population of 40 patients with ulcerative colitis was also assessed.The prevalence of an abnormal serum B12 concentration in patients with CD was 18.4% (95% confidence interval [CI] 13.1–23.8%) compared with 5% (95% CI, 0–11.8%) (P = 0.035) in ulcerative colitis controls. Risk factors for B12 deficiency in patients with CD included prior ileal (odds ratio [OR], 7.22; 95% CI, 1.97–26.51) or ileocolonic (OR, 5.81; 95% CI, 2.09–16.12) resection and the need for ongoing medical therapy (OR, 2.59; 95% CI, 1.03–6.47). Neither disease location nor duration was independently associated with the risk of B12 deficiency.Vitamin B12 abnormalities are common in patients with CD and patients with a prior ileal or ileocolonic resection are at particular risk. Routine screening for B12 deficiency in patients with CD is warranted.