OBJECTIVE: To compare the effectiveness and costs of care for nifedipine-CC and amlodipine when used for initial management of uncomplicated hypertension. METHODS: A retrospective analysis was conducted using outpatient pharmacy, provider, and hospital discharge claims records of continuously eligible Pennsylvania Medicaid patients started on either drug in 1994 without prescriptions for other antihypertensive agents or reported cardiovascular complications in the eight months prior to initial nifedipine-CC or amlodipine prescription. Comparison of three indicators of change in prescriptions were evaluated to provide information on medication effectiveness. Chi-square tests of association were conducted to evaluate effectiveness indicators while linear regression was utilized to compare costs. RESULTS: Patients satisfying inclusion/exclusion criteria who received nifedipine-CC (n=151) or amlodipine (n=316) had similar demographic characteristics and levels of comorbidity. A slightly greater percentage of patients started on nifedipine-CC had prescription records consistent with cross-over to a different calcium channel blocker (15.3% vs. 10.3%) while a greater percentage of patients started on amlodipine had records consistent with cross-over to another class of antihypertensive agent (7.3% vs. 13.2%). In adherent patients, other antihypertensive drugs were added to each regimen to a similar extent and no differences were found in adverse events that were reported. Total pharmacy costs were determined to be significantly higher (p<0.0001) in patients started on amlodipine ($2536 higher in patients with the most comorbidity to $293 in the least). CONCLUSIONS: The results suggest these drugs have similar effectiveness and that physicians’ drug preferences can have important effects on total pharmacy costs.