This study was conducted to compare the antihypertensive efficacy and safety of lercanidipine with those of lacidipine and nifedipine gastrointestinal therapeutic systems in patients aged 65 years or above with mild-to-moderate hypertension. Patients were randomized to receive lercanidipine 5 mg, lacidipine 2 mg, or nifedipine 30 mg for 24 weeks. After 2 weeks, the dose was doubled in non-responding patients. At 24 weeks, blood pressure was significantly reduced in the three treatment groups. The decrease in systolic blood pressure was similar in all three groups. The decrease in diastolic blood pressure in the lercanidipine group (-18.3 mmHg) was comparable to that in the nifedipine group (-17.7 mmHg), but exceeded that in the lacidipine group (-16.6 mmHg). The incidence of adverse drug reactions (ADRs) was lowest in the lercanidipine group (19.4%) compared with the nifedipine group (28.4%) and the lacidipine group (27.1%). In particular, edema was least frequent in the lercanidipine group (2.8%) compared with the lacidipine group (7.5%) and the nifedipine group (10.1%). These data demonstrate that lercanidipine is effective in lowering blood pressure in older adult hypertensive patients while maintaining a superior tolerability and safety profile.