Objective: The prostate-specific antigen density (PSAD) is an accessory tool when suspecting prostate cancer. Multiparametric magnetic resonance imaging (mpMRI) of the prostate has a high rate of false negatives. The aim of this study is to evaluate the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) when adding the PSAD and negative or equivocal mpMRI.Material and methods: A retrospective study that included prostate biopsies performed using a transperineal approach and guided by ultrasound between 2015 and 2019 was conducted. Clinically significant prostate cancer (csPCa) was defined as Gleason score ≥3+4. The population was divided into groups according to the PSAD level-≤0.15 and >0.15. Sensitivity, specificity, NPV, and PPV of mpMRI were calculated.Results: A total of 292 patients were included; 12.1% (4/33 patients) of the negative mpMRI group presented csPCa, and only 7 in the equivocal mpMRI group presented csPCa. NPV and sensitivity were 91.15% and 90.5%, respectively. In the positive mpMRI group, 53.7% (96/179) had csPCa, with a PPV of 53.6% and specificity of 55.3%. Of the patients with PSAD ≤0.15, 23 (16.54%) presented csPCa. All of them presented a positive mpMRI. All patients with a negative or equivocal mpMRI and a PSAD ≤0.15 presented a clinically non-significant tumor or benign result. The addition of this tool to mpMRI resulted in 100% sensitivity, 69% specificity, and 34.8% PPV.Conclusion: In our series, PSAD ≤0.15 increased the NPV in negative or equivocal mpMRI, and through this unnecessary prostate biopsies could be avoided.