OBJECTIVES: Guidelines (JNC VII; ESH-ESC) recommend treatment with two or more antihypertensives to reach BP goals. This study examined the "real-world" effectiveness on BP outcomes for newly diagnosed hypertensives treated with triple-therapy (valsartan-amlodipine-HCTZ) as compared to mono-therapy (amlodipine). METHODS: A retrospective review of an ambulatory electronic medical record (EMR) database of US patients was conducted. Hypertensive adults were identified on the medications of interest. Newly diagnosed hypertensive had no diagnosis for hypertension or antihypertensive medications in the 13 months prior to the index date (first mention of the medications of interest). Baseline BP reading was obtained within 14 days of the medication start date and a post-BP > 30 days but < 365 days after. Mean change in BP and percentage of patients attaining BP goal were calculated. A sub-analysis of stage 1 and 2 hypertensives was also conducted. RESULTS: There were 72 mono-therapy and 249 triple-therapy patients identified. Baseline demographics were similar (mean age, gender, comorbid diabetes). No statistical difference was observed in baseline BPs (mono-therapy 156/86; triple-therapy 154/85). Triple-therapy patients experienced statistically significant higher levels of BP goal attainment (49.5% for triple-therapy; 27.6% for mono-therapy) and statistically significant greater reductions in BPs. Mono-therapy patients achieved modest reductions in SBP [5 mmHg (95% CI: -0.84, 10.84) and DBP [4 mmHg (95% CI: 0.85, 7.15)]. Triple-therapy patients experienced greater reductions in SBP [16 mmHg (95% CI: 12.53, 19.47)] and DBP [7 mmHg (95% CI: 5.14, 8.86)]. The BP reductions with triple-therapy were even greater in stage 2 hypertensives. [N=109; SBP 33 mmHg (95% CI: 27.94, 38.06); DBP 14 mmHg (95% CI: 11.04, 16.96)]. CONCLUSION: Current guidelines recommend combining hypertensive medications with different mechanisms of action to achieve BP control. Utilizing an EMR database of predominantly primary care patients, this study demonstrates the "real-world" effectiveness of triple-therapy with valsartan, amlodipine and HCTZ.