BACKGROUND: The traditional treatment of cobalamin deficiency anemia is performed by intramuscular injections. However, it has been suggested that oral replacement of cobalamin is also effective as an intramuscular injection. We studied the effectiveness of oral mecobalamin treatment in patients with cobalamin deficiency. METHODS: Patients with newly diagnosed cobalamin deficiency (<200 pg/mL) or who were previously maintained on intramuscular injection were given 2,000 microgram of oral mecobalamin daily. RESULTS: Sixteen patients were enrolled. The common causes of cobalamin deficiency were total gastrectomy (75%) and pernicious anemia (12.5%). Twelve patients received oral mecobalamin, except for four patients who were lost from follow-up after initial diagnosis. The mean pretreatment values of serum cobalamin and hemoglobin level were 58.3+/-21.9pg/mL and 8.1+/-1.9g/dL, respectively. After one, two, and six months of oral therapy, the respective mean values were 1,691.8+/-260.4pg/mL, 1,085.8+/-1,110.3pg/mL and 990.2+/-249.8pg/mL of serum cobalamin, and 10.4+/-1.3g/dL, 11.3+/-2.2g/dL and 12.1+/-2.3g/dL of hemoglobin. Initially elevated serum homocysteine were normalized after one month of oral therapy. Symptoms such as glossitis were relieved rapidly by oral treatment. CONCLUSION: High-dose oral mecobalamin supplement was a simple and effective treatment in patients with cobalamin deficiency, especially in total gastrectomized patients.