The role of obesity in prostate cancer etiology remains controversial. A recent report suggested that obese men younger than age 60 may have a lower risk of developing prostate cancer than men the same age who are not obese. The current study used a nested, matched case-control study design and data collected in the General Practice Research Database between January 1991 and December 2001 to assess the association between body mass index (BMI) and the risk of incident prostate cancer. Seven hundred and thirty cases of prostate cancer with adequate information on BMI were identified and matched to 2740 controls on age, sex, general practice, and index date. Obese men (BMI > or = 30.0 kilograms [kg]/square of height in meters [m(2)]) were at lower risk of developing prostate cancer (AOR=0.78, 95% CI: 0.56, 1.09) compared to normal weight men (BMI=23.0-24.9 kg/m(2)), and the data best fit an inverse quadratic model for the relation between BMI and the risk of prostate cancer. This study provides modest support for a protective association between obesity and the risk of incident prostate cancer.