Objective: Obesity and diabetes have been associated with liver cancer. However, recent US-based studies have suggested a lack of association between obesity and liver cancer among blacks and women. Methods: We conducted a nested case-control study within the Multiphasic Health Checkup (MHC) cohort of Kaiser Permanente Northern California (KPNC) members. Liver cancer was diagnosed using the KPNC Cancer Registry. Detailed self-administered questionnaires and a standardized examination that included measurement of height and weight and a 1-h glucose tolerance test were completed prior to diagnosis of liver cancer for cases (n = 450) and matched controls (4489). Height and weight were utilized to calculate BMI (kg/m(2)) as a measure of adiposity: underweight (15-<= 8.5 kg/m(2)), normal weight (18.5-<= 25 kg/m(2)), overweight (25-<= 30 kg/m(2)), and obese (>= 30 kg/m(2)). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between BMI, diabetes, and serum glucose with subsequent incidence of liver cancer, in models that were stratified by birth cohort, race/ethnicity, and sex. Results: Compared to normal weight individuals, obese individuals had a 2.4-fold increased risk of liver cancer (OR = 2.38, 95% CI: 1.68-3.36), and overweight individuals had a 32% increased risk (OR = 1.32, 95% CI: 1.03-1.70). This association did not differ when stratified by birth cohort, race/ethnicity, or sex (pint > 0.05). Among blacks and women, obesity was associated with at least a 2-fold increased risk of liver cancer (OR = 2.29, 95% CI: 1.22-4.28 and OR = 2.00, 95% CI: 1.14-3.52, respectively). More moderate increased odds ratios were noted for diabetes (OR = 1.28, 95% CI: 0.65-2.54) and serum glucose >= 200 mg/dL (OR = 1.63, 95% CI: 0.48-5.55), although the results did not attain statistical significance. Conclusion: In summary, our finding of a positive association between obesity and liver cancer suggests that a higher BMI may increase the risk of liver cancer in the US, for both sexes and all race/ethnicities. Published by Elsevier Ltd.