OBJECTIVES: To compare the cost-effectiveness for treatment of mild and moderate hypertension using either amlodipine or enalapril in the United States. The study is based on data from a randomized controlled clinical trial, conducted with 461 patients. METHODS: We used the raw data from a one-year, double blind clinical trial of amlodipine versus enalapril to quantify the treatment dosages associated with each patient group. The amlodipine group consisted of 231 patients, and the enalapril group included 230 patients. Within the clinical trial, there were no between group significant differences for age, gender, concomitant medications and current illness at randomization. Mean dosages of amlodipine and enalapril, as well as the frequency and dosage of diuretic use, were calculated between groups based on age, gender and study phase, and were used to estimate the cost of treatment. Efficacy and adverse event rates were also calculated for each group to compare the outcomes of the therapy. RESULTS: Amlodipine ($551.62 per patient annual drug treatment cost) was less expensive in treating the hypertensive patients within the study as compared to enalapril ($663.48 per patient annual drug treatment cost). Furthermore, a drug price sensitivity test found that with as much as a 17% reduction in the cost of enalapril, amlodipine would remain a lower or equivalent treatment in terms of cost. The mean final visit dose amounts of drug per patient were 7.2 mg/day for amlodipine, and 28 mg/day enalapril. The total reduction in sitting DBP was 16.9 mmHg with amlodipine and 16.2 mmHg with enalapril. However, significantly (p<0.05) more patients in the enalapril group (n=46, 20%) required the use of a diuretic (HCTZ) to attain control of DBP than in the amlodipine group (n=27, 11.7%). Finally, there were no significant differences (p<0.05) in adverse events between groups (amlodipine = 21.2%; enalapril = 17.4%). Yet, the type of adverse event differed by drug where a significant effect (p<0.001) of amlodipine and edema (15.2%) was found, and a significant effect (p<0.001) for enalapril and cough (7.4%) was found. CONCLUSION: This study suggests that amlodipine is a less costly therapy compared to enalapril, and hence a potentially more cost-effective treatment for mild and moderate hypertension.