Background: In laboratory research, nicotine administration is associated with increases in blood pressure. In epidemiologic research, however, the amount of reported cigarette smoking has no consistent relation with blood pressure. The objective of this study was to examine the relation of a nicotine metabolite (salivary cotinine) to systolic and diastolic blood pressure in current smokers being screened for entry to a clinical trial. Methods and Results: Data were obtained from 5164 middle-aged cigarette smokers during screening for the Lung Health Study. Multiple linear regression was used to examine the association of salivary cotinine and number of cigarettes smoked per day to systolic and diastolic blood pressure with age, body mass, years of education, alcohol intake, and recent caffeinated beverage use controlled in all analyses. Although smoking frequency was unrelated to blood pressure, salivary cotinine was related to greater systolic blood pressure in both men and women and greater diastolic blood pressure in men. Conclusions: The association between salivary cotinine and blood pressure in these analyses suggests that long-term nicotine exposure may be related to modest elevations in blood pressure in cigarette smokers.