Abstract Background: A number of previous studies have suggested that coffee intake is associated with reduced risk of liver cancer and chronic liver disease. However, most prospective studies were conducted in Asian populations where Hepatitis B virus (HBV) and Hepatitis C viruses (HCV) are the dominant risk factors. Prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, individuals prepare coffee in different ways, yet despite known effects of preparation on the constituents found in coffee, it is unknown whether preparation affects disease associations. Methods: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was a double-blind, placebo-controlled trial of α-tocopherol and β-carotene supplementation, set in a population of Finnish male smokers aged 50-69. Among the 29,133 men enrolled at baseline, 27,037 men recorded their coffee consumption and were followed for up to 24 years for incident liver cancer or mortality from chronic liver disease among other outcomes. Information on the method of coffee preparation was available for 20,737 men. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. We used an 8 ounce cup as our unit of analysis. Results: Coffee intake was inversely associated with incident liver cancer (RR per cup/day=0.82, 95% CI=0.73-0.93; RR for intake of ≥4 cups/day vs. intake of >0-<1 cup/day=0.53, 95% CI=0.30-0.95, p-trend across categories=0.0007) and mortality from chronic liver disease (RR per cup/day=0.55, 95% CI=0.48-0.63; RR for intake of ≥4 cups/day vs. intake of >0-<1 cup/day=0.08, 95%CI=0.03-0.18, p-trend<0.0001). Inverse associations persisted in those without diabetes, HBV and HCV negative cases and in analyses stratified by alcohol, smoking dose, and serum cholesterol. Among those with information on coffee preparation, we observed similar associations for those drinking boiled or filtered coffee. Conclusions: Intake of both boiled and filtered coffee was associated with reduced risk of incident liver cancer and mortality from chronic liver disease in the ATBC cohort, suggesting that drinking coffee may have benefits for the liver, irrespective of how it is prepared. Citation Format: Gabriel Y. Lai, Stephanie J. Weinstein, Demetrius Albanes, Philip R. Taylor, Katherine A. McGlynn, Jarmo Virtamo, Rashmi Sinha, Neal D. Freedman. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4828. doi:10.1158/1538-7445.AM2013-4828 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.