The pressure pulse does not have the same amplitude in central and peripheral arteries, but it is amplified toward the periphery; the degree of this amplification depends principally on wave reflection. Despite the conventional clinical and epidemiological focus on peripheral pressures, the most physiologically relevant pressures for both cardiac and vascular effects are central pressures. The reflected wave contributes differently in the configuration of the peripheral and central pressure waveform. Therefore, we hypothesized that agents that alter wave reflections could have an unequal effect on central and peripheral pressures in hypertensive patients. Thus, the effect of caffeine was investigated in 10 hypertensive subjects according to a randomized, placebo-controlled, double-blind, crossover design. Central aortic pressures and wave reflection were assessed with applanation tonometry and pulse wave analysis. After caffeine, augmentation index and augmented pressure increased by 4.6%, (P<0.005) and 5.7 mm Hg (P<0.001), respectively, indicating increased effect of wave reflection from the periphery. The increase in aortic systolic pressure was greater compared with that in radial artery pressure at 30 minutes (25%) and marginally greater at 60 minutes (21%). Furthermore, the increase in aortic pulse pressure was greater at 30 and 60 minutes (34% and 40%, respectively). The intensified reflected wave after caffeine was largely responsible for the disparate effect between central and peripheral pressures by boosting the peak of the central and not of the peripheral waveform. This study shows that pressure-altering agents might affect central pressures more than is apparent from the corresponding upper limb values because of the concomitant changes in wave reflection.