Objective: To prospectively evaluate the diagnostic yield of 12 versus 15 core ultrasound-guided needle prostate biopsy protocol for detection of prostate cancer. Patients and Methods: 244 patients were prospectively randomized to undergo 12 (group A), or 15 (group B) biopsies. The cancer detection rate was compared between these groups and within group B. Results: There were no differences in the age, PSA, prostate volume or Gleason score of diagnosed cancers between groups. 113 (46%) of all patients were found to have carcinoma. The number of cancers diagnosed in each group was: 63 (51.6%) in group A, and 50 (41.0%) in group B. In both groups, performing 12 biopsies increased the number of cancer cases identified by around 10% compared to 6. The frequency of cancer cases increased when 15 biopsies were performed, but not significantly (1.7%). The probability of finding a cancer after 12 biopsies was the same as after 15 biopsies (p = 0.125, McNemar’s test). Conclusions: There was no advantage in increasing the number of biopsy cores from 12 to 15 for the diagnosis of prostate cancer in men with an elevated PSA but normal digital rectal examination.