OBJECTIVES: Single pill combinations (SPC) are associated with improved adherence and persistence in hypertensive (HTN) populations. The evidence is not available for three drug SPC Exforge HCT. This study investigated if Exforge HCT is associated with improved 12-month persistence and adherence in adult hypertensive (HTN) patients.  METHODS: The study included adults (18 yrs. or older) HTN patients covered by commercial and Medicare Supplemental insurance in the Truven MarketScan database with an HTN diagnosis between October 2009 and December 2011. At least two filled prescriptions for Exforge HCT or two periods of minimum 15 days of concurrent use of amlodipine, valsartan and hydrochlorothiazide (FC cohort) were required. Patients were continuously enrolled at least 12 months before and 12 month after the index prescription and had valsartan initial dose of 160 or 320 mg/day. Adherence was measured with proportion of days covered (PDC) and medication possession ratio (MPR). Persistence was defined as no treatment gap greater than 30 days. Chi-Square tests and independent sample t-tests were used after adequate propensity score matching (PSM) (absolute standardized differences <0.1) using demographics, comorbidities, pre-index health care utilization , pre-index costs and valsartan initial dose.  RESULTS: Exforge HCT patients (N=9,221) had better unadjusted outcomes compared to FC patients (N=1,884): higher MPR (81.6% vs 77.0%), PDC (70.0% vs 60.6%) and persistence (42.7% vs 23.6%) (all p<0.0001). After risk-adjustment with PSM, Exforge HCT patients also exhibited better outcomes compared to FC patients: higher adherence (85.7% vs 77.0%), higher PDC (73.8% vs 60.6%) and persistence (46.8% vs 23.6%) (all p<0.0001). More patients had MPR>80% in the Exforge HCT cohort (72.9% vs 57.5%, p<0.0001). CONCLUSIONS: Real-world data indicate that Exforge HCT is associated with improved adherence and persistence compared to amlodipine/valsartan/hydrochlorothiazide FC. These data should be considered by stakeholders engaged with optimizing outcomes of HTN patients.