OBJECTIVE: While a "class effect" is often attributed to ACE-Inhibitor (ACE-I) therapy in hyptertension, pharmacokinetic and pharmacodynamic differences exist between agents for endpoints such as trough:peak ratio and lipophilicity. Agents with these clinical advantages may enable patients to more consistently achieve and maintain low blood pressure (BP) than agents with lower trough:peak ratios and poorer lipophilicity. This study assessed the economic implications of these clinical benefits in the management of hypertension. METHODS: A literature-based decision model was developed to project the relative costs and effectiveness over one year of four commonly prescribed ACE-Is (benazepril, lisinopril, ramipril and quinapril) versus trandolapril from the perspective of a typical managed care plan (MCO) with 100,000 members, of whom 1,700 were projected to take ACE-Is for hypertension. Therapy effectiveness was measured as the proportion of patients achieving BP control. Controlled patients were assumed to incur substantially lower non-drug costs ($599-$1,048) than uncontrolled patients ($4,449-$17,751). Drug costs reflected the price and actual dose taken based on national prescription data. In the most conservative scenario, all therapies were assumed to result in identical levels of BP control (59%). In the least conservative scenario, it was assumed that patients taking therapies with either poorer lipophilicity or lower trough: peak ratios would be less frequently controlled (38%). RESULTS: Trandolapril saved between $48,000 to $235,000 compared to other ACE-Is in the most conservative scenario. In the least conservative scenario, the cost of therapies with lower BP control increased significantly and exceeded that of trandolapril by $1.8 to $2.0 million. CONCLUSIONS: In both scenarios, trandolapril saved costs relative to comparator ACE- I therapies. These savings were driven by trandolapril's lower price and the clinical benefits anticipated to result from its lower trough:peak ratio and better lipophilicity. These benefits include more consistent BP control and reduced need for multiple dosing.