Systolic hypertension often requires combination therapy. Few data exist comparing angiotensin receptor blocker plus diuretic therapy with other combinations in older patients. In a prospective, randomized, open-label, blinded-end point trial, patients (≥60 years of age) with predominantly systolic hypertension received telmisartan 40–80 mg or amlodipine 5–10 mg for 8 weeks, before the addition of hydrochlorothiazide (HCTZ) 12.5 mg for a further 6 weeks. Twenty-four-hour ambulatory blood pressure monitoring showed that telmisartan plus HCTZ (n =448) and amlodipine plus HCTZ (n =424) changed systolic blood pressure for the last 6 hours of the dosing interval by −18.3 and −17.4 mm Hg, respectively (p =0.2520). Over the 24-hour period, telmisartan plus HCTZ was superior (−19.3 and −17.2 mm Hg, respectively; p =0.001) and provided higher systolic control rates (65.9% and 58.3%, respectively; p =0.0175). Adverse events (41.2% and 53.7%, respectively) and discontinuations (5.0% and 11.3%, respectively) were lower (p<0.0001) with telmisartan than with amlodipine, mainly due to peripheral edema (1.2% and 24.3%, respectively).