OBJECTIVES: To compare the effectiveness of two widely prescribed agents, amlodipine and valsartan, in blood pressure lowering and control in a multi-center ambulatory practice setting. METHODS: All adult hypertensive patients were identified from 1998 to 2001 from a large commercially available electronic medical record covering over 360,000 US primary care patients. Study patients were required to have initiated therapy with either amlodipine or valsartan and to have at least one BP measurement within 6 months preceding and 12 months following the index date. Mean change in systolic blood pressure (SBP) and rates of JNC VI BP goal attainment were compared using multivariate statistics. RESULTS: One thousand one hundred seventy-five amlodipine and 512 valsartan patients met criteria. Baseline SBP was 159.5 mmHg for amlodipine; 159.9 for valsartan. Overall, amlodipine was associated with an adjusted mean change of -16.6 mmHg in SBP (95% CI -17.7, -15.5) vs. -13.4 mmHg for valsartan (95% CI -15.1, -11.7; p=0.002). Approximately 43% of amlodipine patients achieved JNC VI goal vs. 33% in the valsartan treated cohort (p=0.030). Among patients on complex antihypertensive regimens (2 or more agents), amlodipine was associated with an adjusted mean change of -16.6 mmHg (95% CI -18.5, -14.8) vs. -10.0 mmHg for valsartan (95% CI -12.8, -7.2; p<0.001). Within this subgroup, JNC VI goal attainment was 43% vs. 36% for amlodipine vs. valsartan (p=0.095). CONCLUSIONS: In monotherapy and in combination, amlodipine demonstrated both a statistically significant and clinically meaningful improvements in SBP change and JNC VI goal attainments vs. valsartan, particularly among patients on complex antihypertensive regimens. Although these data must be interpreted within the limitations of the observational study design, this study suggests that amlodipine may be used in a variety of therapeutic combinations and among a broad spectrum of hypertensive adults to improve SBP control and goal attainment.