Background: An elevated plasma homocysteine level is an established risk factor for cardiovascular disease. Vitamin B12 plays a key role in homocysteine metabolism and could be the main factor in causing cardiovascular disease as well. Objectives: The aim of this study was to assess whether vitamin B12 deficiency or hyperhomocysteinaemia is associated with recurrent cardiovascular events. Methods: Overall, 211 patients discharged alive from our Coronary Care Unit were recruited from February till May 1998. Serum vitamin B12 and plasma homocysteine levels were measured in fasting blood samples. Patient characteristics, medical information and cardiovascular risk factors were assessed from medical files. Patients were followed for 5 years and the prevalence of cardiovascular mortality and morbidity was collected. Results: In the follow-up period of 810 person-years, 48 (21%) of the patients experienced a nonfatal recurrent cardiovascular event and another 14 (7%) died of a cardiovascular cause. Among those with ischaemic heart disease at discharge, no difference in survival was found between the patients with a low (<250 pmol/l) or a high vitamin B12 level (p = 0.21). In patients with hyperhomocysteinaemia (>16 µmol/l), an increased risk of a recurrent cardio vascular event (p = 0.05) in comparison to those with normal plasma homocysteine levels was proven (adjusted hazard ratio of 2.22 (95% CI: 1.40–3.04). Conclusions: In conclusion, high plasma homocysteine concentration, but not a low serum vitamin B12 concentration, increases the risk of cardiovascular morbidity and mortality in patients with ischaemic heart disease.