Recent studies have suggested that multiparametric magnetic resonance imaging (MRI)/ultrasound (US) fusion-guided prostate biopsy can detect more clinically significant prostate cancers, which could impact patient management. As many of the studies evaluating MRI/US fusion-guided prostate biopsy were conducted in specialized quaternary care centers, the question remains whether this technology is transferable to general practice. Our study assesses the diagnostic ability of MRI/US fusion-guided prostate biopsy compared with standard biopsy in the new era of prostate cancer Grade Grouping. We reviewed our prostate biopsy database evaluating men who underwent MRI/US fusion-guided prostate biopsy with concurrent standard 12-core extended-sextant biopsy. Patient demographics and pathologic findings were reviewed. All patient biopsies were performed by 1 of 2 urologic oncologists. Tumors were given a Grade Group for each biopsy based on the core with the highest grade in each case. A total of 191 patients underwent MRI/US fusion-guided biopsy with concurrent 12-core extended sextant biopsy, with a cancer detection rate of 56%. The average number of biopsy cores obtained via the targeted approach was significantly less than those obtained by standard biopsy, 4.8 cores versus 12 cores, respectively, P<0.001. There was no difference in cancer detection between targeted and standard biopsy, 41.4% and 49.2%, respectively, P=0.15. However, when comparing the 2 techniques, the degree of detection of ≥Grade Group 3 tumors significantly favored targeted biopsy over standard biopsy (P=0.009). MRI/US fusion-guided prostate biopsy is equivalent to the standard-of-care 12-core biopsy in terms of cancer detection and superior in detecting higher grade disease.