Purpose: We assessed the effects of medication with dutasteride on serum prostate-specific antigen (PSA), PSA density (PSAD) and prostate volume to avoid unnecessary biopsies. Materials and Methods: Between 2005 and 2007 patients with serum PSA level of 4~10 ng/ml were recruited in this prospective study. Patients were treated with 0.5 mg of dutasteride once daily for 3 months. PSA, PSAD and prostate volume were measured at baseline and at the end of treatment. The patients with a high PSA level (> or =4 ng/ml) after medication with dutasteride had a prostate biopsy. The patients were divided as group I (prostate cancer; n=29) and group II (benign disease; n=55). We compared the changes of serum PSA, PSAD, and prostate volume change between two groups. Results: In group I, PSA, PSAD and prostate volume decreased from baseline means of 8.16 ng/ml, 0.23 ng/ml/cm3 and 46.81 cc to 5.69 ng/ml, 0.18 ng/ml/cm3 and 40.41 cc. The difference in PSA, PSAD and prostate volume was -0.2%, -2.1% and -3.6% for group I. On the contrary, in group II, PSA, PSAD and prostate volume decreased from baseline means of 7.65 ng/ml, 0.16 ng/ml/cm3 and 56.48 cc to 4.48 ng/ml, 0.11 ng/ml/cm3 and 51.35 cc. The difference in PSA, PSAD and prostate volume was -41.4%, -33.3% and -9.1% for group II. When 4.83 ng/ml and 0.15 ng/ml/cm3 were chosen as the PSA and PSAD cutoff levels after treatment with dutasteride, unnecessary biopsies could be avoided effectively. Conclusions: These data suggest that the magnitude of changes in serum PSA and PSAD after 3 months of dutasteride challenge could be useful to avoid unnecessary prostate biopsies in patients with elevated PSA level.