Epidemiologic studies of statin use in relation to prostate cancer risk have been inconclusive. Recent evidence, however, suggests that longer-term use may reduce risk of more advanced disease. The authors conducted a population-based study of 1,001 incident prostate cancer cases diagnosed in 2002-2005 and 942 age-matched controls from King County, Washington, to evaluate risk associated with statin use. Logistic regression was used to generate odds ratios for ever use, current use, and duration of use. No overall association was found between statin use and prostate cancer risk (odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2 for current use; OR = 1.1, 95% CI: 0.7, 1.8 for >10 years' use), even for cases with more advanced disease. Risk related to statin use, however, was modified by body mass index (interaction p = 0.04). Obese men (BMI > or =30 kg/m2) who used statins had an increased risk (OR = 1.5, 95% CI: 1.0, 2.2) relative to obese nonusers, with a stronger association for longer-term use (OR = 1.8, 95% CI: 1.1, 3.0 for > or =5 years' use). Although statin use was not associated with overall prostate cancer risk, the finding of an increased risk associated with statin use among obese men, particularly use for extended durations, warrants further investigation.