Objective <p>The present study aims to evaluate the incidence and risk factors of postoperative pathological upgrading in patients with biopsy Gleason score 6(bGS6), and to explore whether relevant clinical parameters can stratify patients at high risk of upgrading.</p> Materials and methods <p>A total of 241 patients who were diagnosed with bGS6 and subsequently underwent RP at our center were included in this study. The clinical baseline parameters of the patients were collected, and the predictive factors for postoperative pathological upgrading were identified using logistic regression analysis.</p> Results <p>A total of 96 patients (39.8%) with bGS6 experienced Gleason score upgrading after radical prostatectomy(RP). Multivariate logistic regression analysis indicated that prostate specific antigen density (PSAD) &gt; 0.21 ng/ml² (<i>p</i> = 0.003, OR: 3.403) and Prostate Imaging-Reporting and Data System(PI-RADS) 4–5 (<i>p</i> &lt; 0.001, OR: 3.887) were risk factors for the upgrading after RP. In the present cohort, when patients with bGS6 met both PI-RADS 4–5 and PSAD &gt; 0.21 ng/ml², the probability of postoperative Gleason score upgrading was 78.7%; when at least one of the risk factors was fulfilled, the upgrading probability was 37.7%; if none of the risk factors were met by the patients, the probability of remaining Gleason score 6 of postoperative was 84.4%.</p> Conclusion <p>For patients with bGS6 who are at intermediate or low risk, PSAD &gt; 0.21 ng/ml2 and PI-RADS 4–5 are risk factors for the upgrading after RP. The risk stratification model constructed based on these two parameters allows for the preliminary differentiation of postoperative upgrading risk levels among patients in this cohort. This finding regarding the association between the model and upgrading risk provides a reference basis for future prospective validation studies.</p>