Caffeine acutely increases blood pressure and peripheral vascular resistance, in part because of sympathetic stimulation. Its effects on large artery properties are largely unknown. In a double-blind crossover study, 7 healthy subjects 26+/-2.6 years of age (mean+/-SEM) were studied for 90 minutes while in the supine position on 2 occasions separated by a week in random order after ingestion of 250 mL caffeinated (150 mg) and decaffeinated (<2 mg) coffee. Compared with baseline, arterial stiffness measured by carotid femoral pulse wave velocity increased progressively from 7.2+/-0.41 to 8.0+/-0.6 m/s (P<0.05) at 90 minutes after caffeine intake, an effect that may be independent of changes in blood pressure. In addition, arterial wave reflection, measured by applanation tonometry from the aortic pressure waveform, also increased from -5.7+/-7.6% to 5.28%+/-5.6 (P<0.01). No such changes were seen with decaffeinated coffee intake. Although the integral of the brachial systolic and diastolic blood pressure values over the 90 minutes was larger (P<0.05) after caffeinated than decaffeinated coffee intake, the effect on aortic systolic and diastolic blood pressures was more pronounced (P<0.05) than on the brachial artery. These results show a significant effect of caffeine intake on arterial tone and function and suggest that caffeine acutely increases arterial stiffness.