108 Background: MRI fusion prostate biopsy has been shown to improve detection of clinically significant prostate cancer, however the degree of this benefit is poorly characterized in large clinical trials. Methods: 1750 MRI targeted plus sextant biopsies were performed in 1742 male patients from 2007 to 2017. Patient demographics, PSA, prostate volume, primary and secondary Gleason scores, Johns Hopkins Grade Groups, number of MRI targeted lesions, number of cores obtained, and biopsy yield were recorded. Results: The patient population consisted of men averaging 62.9-year-old (36-86) with a mean PSA 9.6ng/mL, and prostate volume of 59.2 ml. A total of 804 cancers were detected on sextant biopsy and 839 were detected on MRI targeted biopsy. Relative to targeted biopsy, sextant biopsy detected only significantly more Gleason 6 disease (14% vs 21.5%, p < 0.0001) than targeted biopsy. Targeted biopsy detected more Gleason 7 (21% vs 16.6%, p = 0.0009) and Gleason 8-10 (13.4% vs 9.4%). Additionally, Gleason 7 sub-stratification demonstrated substantially more Gleason 4+3 detection in targeted group vs sextant biopsy (4% vs 0.5%, p < 0.0001). When stratified by Grade Group targeted biopsy detected 76% more Grade Group 3-5 cancers (p < 0.0001) and 17.7% less Gleason Group 1-2 cancers (p < 0.0001). Only 1.7% of Grade Group 3-5 cancers were detected on sextant biopsy alone, where as 15.7% of Grade Group 3-5 cancers were detected on targeted biopsy alone. Conclusions: MRI targeted biopsy significantly increases the likelihood of detecting clinically significant cancer and decreases the risk of indolent cancer detection. These finding strongly support the use of MRI targeted biopsy when possible.