Objectives: The study aimed to evaluate associations of prostatic chronic inflammation (PCI) with prostate cancer (PCA) grade groups by the International Society of Urological Pathology (ISUP). Methods: The study evaluated retrospectively 738 cases. The patient population was sampled into 3 groups collecting cases without and with PCA including subjects with lSUP grade group 1 and grade groups 2–5. Results: PCI was assessed in 185 patients (25.1%) and PCA in 361 patients (48.9%) of whom 188 (25.5%) had ISUP grade and 173 (23.4%) had ISUP groups 2–5 tumors. PCI inversely related to ISUP groups (p < 0.0001). In multivariate analysis, the risk of ISUP grade group 1 PCA compared to negative cases associated positively with age (OR 1.042; p = 0.001) but inversely with total prostate volume (TPV; OR 0.965; p < 0.0001) and PCI (OR 0.314; p < 0.0001). Intermediate-high grade tumors associated positively with age (OR 1.065; p < 0.0001), prostate specific antigen (OR 1.167; p < 0.0001), and abnormal digital rectal examination (OR 2.251; p < 0.0001) but inversely with TPV (OR 0.921; p < 0.0001) and PCI (OR 0.106; p < 0.0001). Conclusions: PCI decreased the risk of PCA among ISUP tumor grade groups.