To evaluate the comparative efficacy and cost-effectiveness of various antihypertensive medications in persons aged 35 through 64 years with diastolic blood pressure of 95 mm Hg or greater and no known coronary heart disease, we used the Coronary Heart Disease Policy Model, which is a computer simulation of overall mortality as well as the mortality, morbidity, and cost of coronary heart disease in the US population. From the pooled literature, we estimated the antihypertensive and total cholesterol effects of various antihypertensive regimens. For 20 years of simulated therapy from 1990 through 2010, the cost per year of life saved was projected to be $10,900 for propranolol hydrochloride; $16,400 for hydrochlorothiazide; $31,600 for nifedipine; $61,900 for prazosin hydrochloride; and $72,100 for captopril. Doubling the cholesterol effects of the agents under study did not significantly change their effectiveness because, in general, lowering diastolic blood pressure by 1 mm Hg was equivalent to lowering the cholesterol level by 6%. Although any projection requires multiple estimates, each of which may be open to debate, propranolol appears to be the preferred initial option under most of a variety of alternative assumptions.