Objective: To determine whether clinical or radiological parameters can predict clinically significant prostate cancer (csPC) in patients with the Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions. Patients and Methods: Data were obtained from 247 patients with PI-RADS 3 lesions on mpMRI and who had received a soft-ware guided transperineal/transrectal MRI/transrectal ultrasonography (MRI/TRUS) fusion prostate biopsy with concomitant standard systematic 12-core biopsy following mpMRI in the prostate cancer and prostate biopsy database of Turkish Uroon-cology Association, between 2016 and 2020. The cut-off values of clinical parameters were determined using receiver operating characteristic (ROC) curve analysis. Simple and multiple logistic regression analyses were performed to determine the clinical parameters in predicting csPC. Results: A total of 56 patients (22.6%) had prostate cancer, 23 (9.3%) of whom had csPC. In the lesion-based analysis, cancer detection rates (CDRs) of each lesion in targeted biopsy were found to be 6% and 5% for ISUP GG 1 and ISUP GG >= 2, respectively. In the patient-based analysis, clinically insignificant CDRs were significantly higher in systematic biopsy compared with targeted biopsy, whereas no significant difference was found in terms of clinically significant CDRs (p = 0.020 and p=0.422, respectively). The cut-off values were determined as 48.3 mL (AUC [95% CI] = 0.68 [0.53-0.82]) for prostate volume, and 0.213 ng/mL/mL (AUC [95% CI] = 0.64 (0.51-0.77]) for PSAD in predicting csPC. In the multiple logistic regression analysis, only PSAD was found to be an independent risk factor in predicting csPC (OR [95% CI]: 3.56 [1.15-10.91], p = 0.024). Conclusion: Since PSAD > 0.20 ng/mL/mL was found to be positive independent risk factor in predicting csPC, in the absence of advanced radiological parameters, PSAD could be used for the biopsy decision in patients with PI-RADS 3 lesions.