We evaluated the efficacy and safety of amlodipine besylate alone or in combination with other antihypertensive agents in high-risk hypertensive patients in Spanish primary care. In this 1-year, open-label, prospective cohort study, 7468 patients were treated with amlodipine 5 - 10 mg as a monotherapy or as an add-on therapy to attain blood pressure control (target of < 140/90 mmHg or, in patients with conditions such as diabetes or chronic kidney disease, < 130/85 mmHg). At 12 months, the primary outcome (change from baseline in predicted 10-year coronary heart disease risk) was -8.6%, down from 24.7% at baseline (relative risk reduction, 31.6%). Change in blood pressure from baseline (162.5/95.3 mmHg) was -26.7/-14.6 mmHg, and 38.6% of patients achieved their blood pressure target. In summary, significant reductions in predicted coronary heart disease risk and blood pressure were observed with amlodipine both as a monotherapy and as an add-on therapy. Amlodipine was well tolerated and compliance with treatment was good.