A prospective analysis was conducted to assess the incidence of inflammatory features reported in targeted biopsies of 531 MRI-suspicious lesions with prostate imaging-reporting and data system (PI-RADS) scores of 3 to 5 in 364 men suspected of having PCa. The incidence of inflammatory features in the MRI-suspicious lesions without PCa was 69.6%, compared to 48.1% in those with PCa (p < 0.001). Among the suspicious lesions without PCa, the incidence of inflammatory features ranged from 68.6% to 71.2% across the PI-RADS categories (p = 0.870). Mild chronic prostatitis increased with higher PI-RADS scores, while acute prostatitis decreased, and granulomatous prostatitis was exclusively observed in patients with PI-RADS scores of 4 and 5. The incidence of inflammatory features in the lesions with insignificant PCa (grade group 1) was 66.7%, compared to 42.7% in those with significant PCa (grade group 2 to 5; p = 0.027). The detection of inflammatory features in MRI-suspicious lesions was identified as an independent predictor of a lower likelihood of significant PCa detection, with an odds ratio (OR) of 0.326 (95% CI 0.196-0.541). Mild chronic prostatitis was the only type of prostatitis which was an independent predictor of a lower likelihood of significant PCa, with an OR of 0.398 (95% CI 0.268-0.590). These data suggest that inflammatory features may be considered to be mimickers of significant PCa on MRI.