Mitochondrial DNA 5178 cytosine/adenine (Mt5178C/A) polymorphism is reported to be associated with longevity and to modify the effects of alcohol consumption or coffee consumption on the risk of hypertension in the Japanese population. The objective of this study was to investigate whether Mt5178C/A polymorphism modifies the effects of green tea consumption on blood pressure or risk of hypertension in middle-aged Japanese men. A total of 394 male subjects (age, 53.9±7.9 years; mean±SD) was selected among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as systolic blood pressure (SBP)≥140 mmHg, diastolic blood pressure (DBP)≥90 mmHg, and/or undergoing antihypertensive drug treatment. After adjustment, irrespective of antihypertensive drug treatment, the association between Mt5178C genotype and hypertension was dependent on green tea consumption (P for trend=0.043 and P for trend=0.011, respectively). In particular, among subjects≥50 years old with Mt5178C, excluding those taking antihypertensive drugs, a significant association between green tea consumption and risk of hypertension was observed (P for trend=0.019), and the odds ratio for hypertension was significantly lower in those who consumed≥6 cups of green tea per day than in those who consumed≤1 cup per day (odds ratio=0.167, 95% confidence interval: 0.033-0.832). On the other hand, the association between Mt5178A genotype and hypertension did not depend on green tea consumption. No consistent association between green tea consumption and blood pressure was observed in either genotype. The present results suggest a joint effect for Mt5178C/A polymorphism and green tea consumption on the risk of hypertension in middle-aged Japanese men.