Using a retrospective cohort study of medical and pharmacy claims data, we evaluated medication compliance, persistence, and hypertension-related expenditures among patients who were switched from fixed-dose combination (FDC) to free-combination (FC) antihypertensive therapy. An example of a fixed-dose combination product for hypertension would be a valsartan/HCT tablet, and a free-combination product would be a valsartan tablet plus a diuretic tablet.The 7,224 patients identified from January 2003 to December 2005 were matched, in a 1:1 ratio, by propensity scores to controls who remained on their FC antihypertensive medications. Compliance, defined as a medication-possession ratio, was measured over 12 months. Persistence was measured as the percentage of patients who did not experience a lapse in therapy of more than 30 days since their last prescription refill.The patients continuing with FDC therapy had better persistence (42.5% higher; P < 0.002) and compliance (22.1% higher; P < 0.001), compared with patients who were switched to FC therapy. The 22.1% higher compliance rate for patients continuing the FDC regimen was associated with significantly lower expenditures for hypertension-related health care (P < 0.001) and an estimated 5% reduction in hypertension-related expenditures.