Available in vitro and animal studies have shown cancer protective effects of tea polyphenols. Recent study suggests a greater protective effect of green tea intake on breast cancer risk among women possessing the low-activity associated genotype of the catechol-O-methyltransferase (COMT), which may modulate the metabolism and excretion of tea polyphenols through urine. To determine the effect of COMT genotype on urinary excretion of tea polyphenol metabolites of daily green tea drinkers, a cross-sectional analysis was performed within the Shanghai Cohort Study, a population-based, prospective investigation of diet and cancer in 18,244 men. In addition to an in-person interview, each participant provided a blood and urine sample at baseline. In the present study, COMT genotype (rs4680) and five urinary metabolites of tea polyphenols were determined in 660 cohort subjects who self-identified as daily drinkers of green tea. All urinary tea polyphenol measurements were expressed in units of urinary creatinine. Men possessing the homozygous low-activity associated COMT genotype (LL) exhibited statistically significantly lower urinary levels of individual as well as all of the five tea polyphenol metabolites under study relative to individuals possessing the wild type high-activity associated COMT genotype (HH) or the heterozygous variant genotype (HL). Levels of urinary tea polyphenol metabolites were comparable between men possessing the HH and HL genotypes. The present study demonstrated that men carrying low-activity associated COMT genotype excreted less tea polyphenols from urine, which suggests that they may retain more tea polyphenols in their bodies and derive greater health benefits from green tea intake.