Health care decision-makers require more information on differences in compliance rates associated with alternative classes of antihypertensive drugs and the implications of these differences for health care utilization and costs. We examined medical claims data from the Pennsylvania Medicaid Management Information System to investigate compliance rates for four major antihypertensive drug classes (angiotensin-converting enzyme [ACE] inhibitors, beta-blockers, calcium antagonists, and diuretics) and the health care costs associated with noncompliance. Multivariate analysis was used to relate antihypertensive drug class with compliance and variations in compliance with health care costs. The highest estimated rates of compliance were associated with ACE inhibitors and calcium antagonists, and these rates were significantly greater than with beta-blockers and diuretics. Moreover, poor compliance was associated with higher health care costs. Efforts to increase compliance with antihypertensive drug therapy are needed to improve patient outcomes and reduce health care costs.