Aim To determine clinical risk factors in patients with PI-RADS 3 lesions and prostate-specific antigen (PSA) < 10 ng/mL. Methods In this prospective study, all patients underwent multiparametric magnetic resonance imaging. Following the 2-5 core fusion-targeted biopsy, standard 12-core prostate biopsy was performed in each patient (combined biopsy). The cutoff values were calculated with receiver-operating characteristic analysis. First, univariate logistic regression analysis was used to evaluate the relationship between total eight parameters and prostate cancer. Subsequently, multiple logistic regression analysis was performed to the parameters associated with prostate cancer. Results Two hundred and eighty-eight patients were included in the study. Some clinical parameters are determined to be significant in univariate and multiple logistic regression analyses, including PSA, free/total PSA ratio, PSA density (PSA/total prostate volume), positive family history of PCa, and PI-RADS 3 lesion diameter. Patients were classified between 0 and 5 according to the number of risk factors. While the risk of cancer was 7.1% in patients with one or less risk factors, the PCA rate was 45.2% among patients with all risk factors. Conclusion In patients with PI-RADS 3 lesion and PSA < 10 ng/mL, histopathological results of biopsy can be estimated with higher accuracy using some clinical parameters.