Abstract Purpose To evaluate the Prostate Health Index (PHI) density (PHID) in direct comparison with PHI in a prospective large cohort. Methods PHID values were calculated from prostate-specific antigen (PSA), free PSA and [− 2]proPSA and prostate volume. The 1057 patients included 552 men with prostate cancer (PCa) and 505 with no evidence of malignancy (NEM). In detail, 562 patients were biopsied at the Charité Hospital Berlin and 495 patients at the Sana Hospital Offenbach. All patients received systematic or magnetic resonance imaging (MRI)/ultrasound fusion-guided biopsies. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves comparing areas under the ROC-curves (AUC). The decision curve analysis (DCA) was performed with the MATLAB Neural Network Toolbox. Results PHID provided a significant larger AUC than PHI (0.835 vs. 0.801; p = 0.0013) in our prospective cohort of 1057 men from 2 centers. The DCA had a maximum net benefit of ~ 5% for PHID vs. PHI between 35 and 65% threshold probability. In those 698 men within the WHO-calibrated PSA grey-zone up to 8 ng/ml, PHID was also significantly better than PHI (AUC 0.819 vs. 0.789; p = 0.0219). But PHID was not different from PHI in the detection of significant PCa. Conclusions Based on ROC analysis and DCA, PHID had an advantage in comparison with PHI alone to detect any PCa but PHI and PHID performed equal in detecting significant PCa.