diate/high-grade cancers (GS ≥3 + 4) (50/64 vs. 33/74) using fewer biopsy cores compared with TRUS-bx (p < 0.001). Using an "MRI-targeted-only" approach in men with PI-RADS ≥3 lesions reduced the number of men requiring repeated biopsies by 50%, decreased low-grade cancer diagnoses by 66%, and increased intermediate/high-grade cancer diagnoses by 52%. Conclusions: MRI-targeted biopsies have a high detection rate for significant PCa in patients with prior negative transrectal ultrasound-guided biopsies and preferentially detect intermediate/high-grade compared with low-grade tumors.