In this study, we measured the excretion rate of nicotine and its two major metabolites, cotinine and trans-3'-hydroxycotinine (THOC), in the urine of 25 healthy smokers and 15 smokers who underwent a coronary artery bypass surgery or coronary angioplasty. After 1 day of smoking cessation, urine samples were collected in the morning, before smoking two cigarettes, and then three times after smoking, approximately 4 h apart. The results show that (i) in healthy smokers, nicotine and its two major metabolites were present at high concentration in the first urine sample after smoking, (ii) in smokers with cardiovascular disease nicotine and cotinine were less excreted whereas THOC was more excreted, mainly in the second urine sample. We conclude that this shift in nicotine metabolism may contribute to smoking-induced cardiovascular disease.