Background Concerns persist about the validity of generalized transfer function-derived, aortic blood-pressure measurements during the administration of vasoactive agents in clinical trials. Hence, we compared this transfer-function method with another, which estimates aortic systolic pressure directly from the late systolic shoulder of the radial pressure wave, after administration of placebo, ramipril, or atenolol. Methods We recorded radial pressure pulse waveforms, using a commercially available system, in 30 subjects with ≥1 coronary risk factor in an acute study of ramipril at 10 mg and atenolol at 100 mg. Directly recorded radial and derived aortic pressure pulse waveforms were examined individually and were ensemble-averaged, and the difference between radial and aortic pressure responses was examined. Results The late systolic shoulder response from radial waveforms was reduced by 15.8 mm Hg (SD, 12.2 mm Hg) more with ramipril than with atenolol. This was similar to a difference of 14.6 mm Hg (SD, 11.2 mm Hg) calculated for the aortic systolic pressure response using the transfer-function technique. Ramipril caused a greater reduction in the aortic systolic pressure response (22.2 mm Hg), whereas with atenolol, there was a modest decrease (7.6 mm Hg). The mean difference between aortic systolic pressures measured from direct radial waveforms and from derived aortic pressure between 3 and 5 h after dosing under all circumstances was 1.6 mm Hg (SD, 8.9 mm Hg). Conclusions Central pressure derived from radial pressure waveforms using a generalized transfer function gave similar results for central pressure measured directly from radial waveforms. The hemodynamic benefits of angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and calcium channel blocker over β-blocker antihypertensive therapy in recent trials were confirmed by this study.