ABSTRACTObjectivesTo compare the detection rates for clinically significant prostate cancer (csPCa; grade group 2 or higher disease) using MRI‐targeted biopsy (MRI‐TB) versus systematic biopsy (SB) or their combination, and identify risk factors for detecting csPCa in MRI‐TB with systematic transrectal (TR)/transperineal (TP) biopsies (sTR/TP‐bx) and MRI‐TB with sTP‐bx.MethodsWe retrospectively analyzed 216 patients who underwent MRI‐TB with SB at our hospital between September 2020 and December 2023 and compared clinical characteristics for patients with and without prostate cancer.ResultscsPCa was detected in 132 (61.1%) patients by MRI‐TB with sTR/TP‐bx, in 121 (56.0%) patients using MRI‐TB with sTP‐bx, and in 101 (46.8%) patients using MRI‐TB. Older age, higher PSA density (PSAD), smaller prostate volume, region of interest in the peripheral zone, higher Prostate Imaging‐Reporting and Data System (PI‐RADS), and administration of dutasteride were more common in csPCa cases. A scoring system was constructed based on odds ratios for PSAD, PI‐RADS ≥ 4, and administration of dutasteride; accordingly, the detection rate of csPCa was 20.3% (14/69) in the low‐risk group (RG) and 95.5% (42/44) in high RG for MRI‐TB with sTR/TP‐bx, and 16.7% (12/72) in the low RG and 97.8% (45/46) in high RG for MRI‐TB with sTP‐Bx.ConclusionsThe addition of SB increased the detection rate of csPCa compared with MRI‐TB alone. PSAD, PI‐RADS ≥ 4, and administration of dutasteride significantly affect the detection of csPCa using MRI‐TB with SB and can be used for deciding whether to perform a biopsy or include sTR‐bx with MRI‐TB.