To assess MRI/Transrectal Ultrasound (TRUS) fusion three-dimensional model-guided targeted biopsy (3D-Tb) versus TRUS-guided systematic biopsy (Sb) in detecting overall and high-Gleason-score (≥7) prostate cancer (PCa). Pubmed and Web of science were searched. Studies with men having a suspicious lesion on MRI were included, which were divided into initial biopsy, previous negative biopsy, and mixed groups in meta-analysis. Totally 13 cohorts in 12 studies, with 3,225 men were included. In total population, 3D-Tb and Sb did not differ significantly in the PCa detection rate (43.1 vs. 42.6%, p = 0.36), but after excluding initial biopsy group, the superiority of 3D-Tb became significant (p = 0.01); 3D-Tb had a significantly higher detection rate of high-Gleason-score PCa compared to Sb (30.0 vs. 24.1%, p < 0.05); 3D-Tb plus Sb significantly improved the PCa detection rate based on Sb alone (52.7 vs. 42.6%, p < 0.05). In men with increased serum PSA and/or abnormal DRE and suspicious lesion on MRI but non-previous evidence of PCa, 3D-Tb plus Sb improves the PCa detection rate based on Sb alone. 3D-Tb alone has better performance in detecting high-Gleason-score PCa, and tends to have a higher PCa detection rate in population with previous negative biopsy compared to Sb. © 2017 S. Karger AG, Basel.