Although case-control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self-administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow-up with 170,640 person-years) and Cohort 2 (7 years of follow-up with 284,948 person-years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46-1.09) and 0.58 (0.36-0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high-risk population are needed.