To improve the diagnostic efficiency of prostate cancer(PCa)and reduce unnecessary biopsies,we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen(PSA)density(PZ-PSAD).Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital(Shanghai,China)between January 2012 and January 2018 were retrospectively identified(n=529).Another group of patients with benign prostatic hyperplasia(n=100)were randomly preselected to obtain the PSA density of the non-PCa cohort(N-PSAD).Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging(mpMRI)and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm.Receiver operating characteristic(ROC)curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level,and the area under the ROC curve(AUC)of PZ-PSAD was higher than that of PSA,PSA density(PSAD),and transition zone PSA density(TZ-PSAD).PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography(TRUS)and mpMRI results.When TRUS and mpMRI findings were ambiguous to predict PCa(PIRADS score≤3),PZ-PSAD could increase the positive rate of biopsy from 21.7％to 54.7％,and help 63.8％(150/235)of patients avoid unnecessary prostate biopsy.In patients whose PSA was 4.0-10.0 ng ml-1,10.1-20.0 ng ml-1,and＞20.0 ng ml-1,the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml-2,0.297 ng ml-2,and 1.180 ng ml-2,respectively(sensitivity＞90％).Compared with PSA,PSAD,and TZ-PSAD,the efficiency of PZ-PSAD for predicting PCa is the highest,leading to fewer missed diagnoses and unnecessary biopsies.