Objectives: To analyse the detection rates of primary MRI-fusion transperineal prostate biopsy using combined targeted and systematic core distribution in three tertiary referral centres. Patients and Methods: Multicentre, prospective outcome study of 807 consecutive biopsy-naïve patients having undergone MRI-guided transperineal prostate biopsy as the first diagnostic intervention between 10/2012 and 05/2016. MRI was reported following PI-RADS criteria. 236 patients had 18-24 systematic transperineal biopsies only, and 571 patients underwent additional targeted biopsies either by MRI-fusion or cognitive targeting if PI-RADS ≥3 lesions were present. Detection rates for any and Gleason score (GS) 7-10 cancer in targeted and overall biopsy. Predictive values were calculated for different PI-RADS and PSA density (PSA-D) groups. Results: Cancer was detected in 68% and GS 7-10 in 49% of patients. Negative predictive value of 236 PI-RADS 1-2 MRI in combination with PSA-D ≤0.1 ng/ml/cm3 for GS7-10 was 0.91 (±0.07, 8% of study population). In 418 patients with PI-RADS 4-5 lesions using targeted plus systematic biopsies, the cancer detection rate of GS 7-10 was significantly higher at 71% versus 59% and 61% with either approach alone (p=0.000). For 153 PI-RADS 3 lesions, the detection rate was 31% with no significant difference to systematic biopsies with 27% (p>0.05). Limitations include variability of mpMRI reading and Gleason grading. Conclusion: MRI-based transperineal biopsy performed at high volume, tertiary care centres with a significant experience of prostate mpMRI and image-guided targeted biopsies yielded high detection rates of GS 7-10 cancer. Prostate biopsies may not be needed for men with low PSA-D and a non-suspicious MRI. In patients with high probability lesions, combined targeted and systematic biopsies are recommended.