Objectives: To evaluate the detection rate of clinically significant prostate cancer (csPCa) in Magnetic resonance imaging and ultrasonography (MRI/US) fusion biopsy in patients with biopsy-naive men for varying prostate-specific antigen (PSA) levels. Since MRI can efficiently detect csPCa compared to standard transrectal ultrasound (TRUS) guided biopsy; however, the optimal PSA threshold for its use is unclear. Materials and methods: We retrospectively reviewed those who underwent MRI/US-fusion and standard biopsy from January 2016 to June 2018. Patients were divided into three groups: PSA <4, 4-10, >10 ng/mL. Propensity scoring was performed to balance the characteristics of the different biopsy groups, and the detection rate of csPCa was compared. Results: Data from a total of 670 males were included in the analysis (standard TRUS, n = 333; MRI/US fusion, n = 337). Prior to matching, patients who received MRI/US-fusion biopsy had lower prostate volume. Propensity score matching balanced this characteristic and generated a cohort comprising 195 patients from each group. In the matched cohort, patients with PSA 4-10 ng/mL had a significantly increased risk of csPCa by MRI/US-fusion vs. standard biopsy (35.0% vs. 26.6%, P = 0.033). However, patients with PSA <4 ng/mL had csPCa found by MRI/US-fusion versus standard biopsy (12.0% vs. 16.0%, P = 0.342), whereas, patients with PSA >10 ng/mL had csPCa found by MRI/US-fusion versus standard biopsy (78.0% vs. 80.0%, P = 0.596). In multivariate logistic analysis among patients with PSA 4-10 ng/mL, MRI/US-fusion biopsy (odds ratio: 2.46, 95% confidence interval = 1.31-4.60, P = 0.005) were significantly associated with a detection of csPCa. Conclusions: Detection of csPCa by MRI/US-fusion biopsy is more efficient in patients with biopsy-naive men with PSA 4-10 ng/mL. However, standard TRUS biopsy may identify csPCa in patients with PSA <4 ng/mL and >10 ng/mL, emphasizing the importance of performing a standard biopsy in conjunction with MRI/US-fusion biopsy in such populations. (c) 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).