Purpose We determined the association between statin use and prostate cancer in men who underwent prostate biopsy. Materials and Methods We performed a retrospective cohort study of men who underwent prostate biopsy from 2000 to 2007 at Cleveland Clinic. Statin use was determined using outpatient pharmacy records, and clinical and pathological outcomes were obtained. Multivariate logistic regression analysis to determine the effects of statins (and duration of use) was performed after adjusting for age, body mass index, African-American race, number of cores taken and prostate volume. Results We analyzed data from 4,204 patients, and we identified 3,182 (75.7%) not on statins and 1,022 on statins. Men diagnosed with prostate cancer on statins compared to those not taking statins were less likely to have digital rectal examination positivity (5.3% vs 8.9%, OR 0.7, p <0.01), Gleason score 7 or greater prostate cancer (61.4% vs 72.4%, OR 0.78, p = 0.02) and high volume prostate cancer (27.2 vs 31.4, p <0.01). Moreover statin users had lower prostate specific antigen compared to nonstatin users (5.13 vs 5.98, p = 0.03). Multivariate analysis adjusted risk ratios for prostate cancer diagnosis, high grade prostate cancer (Gleason score 7 or greater) and 3 or more cores positive in statin users were 0.92 (95% CI 0.85–0.98), 0.76 (95% CI 0.67–0.85) and 0.86 (95% CI 0.75–0.97) and only high grade prostate cancer persisted with length of use. Conclusions Statin use was associated with a decreased risk of prostate cancer, less frequent high grade prostate cancer and lower volume of prostate cancer, suggesting that statin use has a protective effect against prostate cancer.