Sesamin, one of the lignans contained in sesame, has been considered to have medicinal effects. It has been reported that sesamin suppressed the development of hypertension in rats. In this study, using a double-blind, cross-over, placebo-controlled trial, we investigated the effect of 4-wk administration of sesamin on blood pressure (BP) in mildly hypertensive humans. Twenty-five middle-aged subjects with mild hypertension were divided into two groups, matched by age and body mass index. Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo (period 1). After a 4-wk washout period, the subjects received the alternative administration for 4 wk (period 2). BP decreased with statistical significance with the administration of sesamin (systolic: 137.6±2.2 to 134.1±1.7 mmHg, p=0.044, diastolic: 87.7±1.3 to 85.8±1.0 mmHg, p=0.045), but little changed with the placebo (systolic: 135.0±1.8 to 135.1±1.7 mmHg, diastolic: 85.9±1.2 to 86.6±1.2 mmHg). In conclusion, 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP. These results suggest that sesamin has an antihypertensive effect in humans. Epidemiological studies suggested that a 2-3 mmHg decrease in BP reduces the rate of cardiovascular diseases; therefore, it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases.