PURPOSE: We investigated the predictive factors in patient with prostate cancer diagnosed by repeat prostate biopsy, where initial prostate biopsy results were negative for malignancy. MATERIALS AND METHODS: Between March 2000 and June 2007, 1280 men with suspected prostatic cancer underwent transrectal ultrasound guided needle biopsy of the prostate, with 148 (11.6%) diagnosed as having prostate cancer. Of 1132 men whose biopsy results were negative for malignancy, 655 whose prostate specific antigen (PSA) was elevated persistently underwent second biopsy, and 462 underwent third biopsy as the same course. Twelve core biopsies were performed in the majority of patients. To determine predictive factors, we evaluated prostate volume, serum PSA, percent free PSA, PSA density (PSAD), transition zone PSAD, PSA velocity (PSAV) and pathological report of previous biopsy between the men with cancer detection and the men with negative biopsy in second and third biopsy. RESULTS: Overall cancer detection rate was 16.3% (208/1280). From the first, second and third biopsies, the cancer detection rate were 11.6, 5.5 and 5.2%, respectively. There were significant differences in percent free PSA, transition zone PSAD, PSAV between cancer and negative biopsy groups after serial repeat biopsies (p<0.05). Multivariate logistic regression analysis revealed that the transition zone PSAD, PSAV, and presence of either atypical small acinar proliferation (ASAP) or high grade prostatic intraepithelial neoplasia (HGPIN) in initial biopsy specimen were significant predictors for prostate cancer diagnosed by repeat biopsy. CONCLUSIONS: Of the men with negative results on the first biopsy, 60 (5.4%) were diagnosed prostate cancer after serial biopsies. The transition zone PSAD, PSAV, and presence of either ASAP or HGPIN in initial biopsy specimen are predictable factors for prostate cancer detection on repeat biopsy.