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BACKGROUND Prostate cancer（PCa） is one of the most common cancers among men. Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging（mp-MRI） have emerged, which may improve the accuracy of detecting clinically significant PCa in recent years.AIM To investigate the diagnostic efficiency of a template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa.METHODS Data from patients with an increasing prostate-specific antigen（PSA） level but less than 20 ng/m L and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed. All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area. A total of 127 patients with complete data were included in the final analysis. A multivariable logistic regression analysis was conducted, and a two-sided P ＜ 0.05 was considered statistically significant.RESULTS PCa was detected in 66 of 127 patients, and 56 cases presented clinically significant PCa. Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa, specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa. A randomized biopsy detected seven cases of PCa negative on targeted biopsy, and four cases had clinically significant PCa. PSA density（OR: 1.008, 95%CI: 1.003-1.012, P = 0.001; OR: 1.006, 95%CI: 1.002-1.010, P = 0.004） and Prostate Imaging-Reporting and Data System（PI-RADS） scores（both P ＜ 0.001） were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone.CONCLUSION This single-centered study proposed a feasible template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy. Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.