AbstractAlthough amlodipine is recommended as the first‐line therapy for the treatment of hypertension, its use is limited by its potential side effects. S‐amlodipine is expected to be able to minimize side effects of amlodipine with a similar antihypertensive effect by removing the malicious R‐chiral form. However, sustainable blood pressure control with S‐amlodipine has not been well established yet. The purpose of the current study was to evaluate ambulatory blood pressure (ABP) profiles before and after a 12‐week treatment of S‐amlodipine. Patients received once‐daily S‐amlodipine 2.5 or 5 mg. ABP during 24 hr and office blood pressure were measured at baseline and after the 12‐week treatment. Primary endpoints were changes of systolic and diastolic 24 hr ABP. After 12‐week S‐amlodipine treatment, mean systolic ABP (‐15.1 ± 16.2 mmHg, p < .001) and diastolic ABP (‐8.9 ± 9.8 mmHg, p < .001) were decreased significantly. Both daytime and night‐time mean systolic BP and diastolic BP were also significantly decreased after the 12‐week treatment. Global trough‐to‐peak ratio and smoothness index after 12‐week S‐amlodipine treatment were .75 and .79 for SBP and .65 and .61 for DBP, respectively. Age ≥65 years (hazard ratio [HR]: 3.13; 95% confidence interval [CI]: 1.67–14.3) and nonalcohol drinking (HR: 3.09; 95% CI: 1.34–7.17) were independent clinical factors for target ABP achievement. Adverse drug reactions (ADR) were developed in 16 (6.4%) patients, including two (.8%) cases of peripheral edema. In conclusion, this study demonstrated the efficacy and safety of S‐amlodipine in patients with uncontrolled essential hypertension.