The advocated SphygmoCor procedure uses a radial-to-aorta transfer function with calibration on brachial instead of radial artery pressure to assess the central pulse pressure. We compared these values with carotid artery pulse pressures obtained from a validated calibration method, assuming mean minus diastolic blood pressure constant throughout the large artery tree. From 44 healthy subjects (21 males; 22 to 68 years) pressure waves were obtained at the radial, brachial, and carotid artery with applanation tonometry. Using the calibration method, radial and carotid artery pressures were assessed from brachial artery waves and pressures. The effect of brachial-to-radial pulse pressure amplification, brachial pulse pressure, mean pressure, age, gender, height, body mass index, and smoking on differences between the 2 methods was assessed. Brachial artery pressure was 118+/-12/72+/-10 mm Hg. SphygmoCor central pulse pressure was 9.7+/-4.6 mm Hg lower (P<0.001) than the carotid artery pulse pressure (33.0+/-6.8 versus 42.7+/-8.9 mm Hg). The difference between the 2 methods strongly depended (P<0.001) on brachial-to-radial artery pulse pressure amplification (5.8+/-5.1 mm Hg; 12+/-11%) and less on brachial artery pulse pressure (P=0.005). After calibration of the radial pressure wave with radial instead of brachial artery pressures, the difference between SphygmoCor central pulse pressure and carotid pulse pressure decreased with 4 mm Hg. The advocated SphygmoCor procedure systematically underestimates the central pulse pressure with brachial-to-radial pulse pressure amplification as important determinant. Therefore, calibration of radial artery pressure waves on brachial artery pressures should be avoided. The underestimation of central aortic pulse pressure caused by the radial-to-aorta transfer function itself is much less than previously reported.