Background: this study evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer. Subjects and Methods: this study was conducted on fifty patients selected from the Urology Department at Ain Shams University Hospitals and scheduled for prostate biopsy after digital rectal examination first catch urine was collected. PCA3 scores were determined using RT-PCR and compared to biopsy outcome. The diagnostic accuracy of PCA3 was compared to total prostate specific antigen and %free prostate specific antigen.Results: the best cutoff for PCA3 was 4.6 folds (RQ). This cutoff had a diagnostic sensitivity of 94.7%, specificity 95% and area under the curve (AUC) was 0.978. Total PSA at the cutoff 10 ng/mL had a diagnostic sensitivity 68%, specificity 70% and AUC was 0.766. At cut off 19%, f/t PSA ratio had a diagnostic sensitivity 38%, diagnostic specificity 90 %, and AUC was 0.529. Conclusions: the PCA3 assay can aid in guiding biopsy decisions. It is superior to total prostate specific antigen and %free prostate specific antigen in predicting initial biopsy outcome, and may be indicative of prostate cancer aggressiveness.