Abstract: The incidence of coronary artery disease (CAD) is increasing at an alarming rate, especially in developing countries, such as India. It is often advocated that a vegetarian lifestyle could reduce the burden of CAD. However, in spite of a majority of Indians being vegetarians, the incidence of CAD is highest in this population. This may be due to deficiency of vitamin B12, a micronutrient, sourced only from animal products.: Herein, we assessed the effect of vitamin B12 with respect to CAD in 816 individuals (368 CAD patients and 448 controls) recruited from a tertiary care center in New Delhi, India.: We found that vitamin B12 levels were significantly lower in CAD patients than in controls (p<0.0001). Also, vegetarians were found to have significantly lower vitamin B12 concentrations (p=0.0001) and higher incidence of CAD (p=0.01). Interestingly, elevated homocysteine levels, a hallmark of vitamin B12 deficiency, was not associated with CAD. In contrast, cysteine levels were significantly higher in CAD patients than in controls (p=0.004).: We believe that, when vitamin B12 is deficient, homocysteine is rapidly metabolized via the transsulfuration pathway leading to increased cysteine levels.Clin Chem Lab Med 2009;47:334–8.