OBJECTIVES: To compare compliance/persistence, healthcare utilization, and costs associated with select antihypertensive single-pill combination (SPC) vs. free combination (FC) therapies among adult hypertension patients at both the national and state level.   METHODS: Adult hypertension patients initiated on SPC or FC with angiotensin receptor blocker (ARB)+calcium channel blocker, ARB+hydrochlorothiazide, or angiotensin-converting enzyme inhibitors+ hydrochlorothiazide were identified in the MarketScan Database (2006-2008). Study outcomes during the 6-month study period included medication possession ratio (MPR), treatment discontinuation rates, inpatient and emergency room (ER) visits, and changes in healthcare costs (study period minus baseline). Multivariate regression models examined the effect of SPC (vs. FC) use and its regional variation on outcomes, controlling for demographics, comorbidities, prescription use, and healthcare utilization during the baseline period (6 months pre-therapy initiation). Regression-adjusted differences in outcomes between SPC vs. FC patients and associated 95% confidence intervals (CIs) were estimated for the average patient in the U.S. and within each state. RESULTS: Adjusting for baseline, SPC patients (N=382,476) demonstrated significantly higher MPR (difference=9.4% [95% CI: 9.2%, 9.5%]) and were less likely to discontinue treatment (odds ratio=0.535 [95% CI: 0.528, 0.542]) than FC patients (N=197,375) nationwide. SPC patients had significantly less hospitalizations and ER visits than FC patients, including 29% fewer cardiovascular-related hospitalizations (adjusted incidence rate ratio=0.71 [95% CI: 0.69, 0.72]). Compared to FC, SPC patients showed significantly greater reductions post-therapy initiation in all-cause medical costs by -$208 (95% CI: -$302, -$114), but larger increases in hypertension-related prescription costs by $53 (95% CI: $51, $55). State-level results were generally consistent in magnitude and trend for compliance and utilization outcomes, with greater regional variation in costs. CONCLUSIONS: SPC was associated with significantly better compliance/persistence and lower frequencies of hospitalizations and ER visits compared to FC in hypertension patients. Larger reductions in medical costs with SPC offset small increases in drug costs.