Background: Focal therapy (FT) has emerged as a promising, organ-sparing alternative to radiotherapy and radical prostatectomy for the management of localized prostate cancer (PCa). Multi-parametric magnetic resonance imaging (mpMRI) is often used to monitor for post-FT tumor recurrence. However, post-treatment mpMRI assessment can be quite challenging due to treatment-related changes and distortion of the prostate gland anatomy. The Prostate Imaging after Focal Ablation (PI-FAB) score was proposed by Giganti et al. in May 2023 as a standardized three-point scale for rating mpMRI sequences to aid in decision for follow-up imaging or biopsy. The purpose of this study is to investigate the performance of this new scoring system in predicting recurrent clinically significant prostate cancer (csPCa), defined as Gleason grade > 1 disease. Methods: Patients with localized PCa who underwent focal laser ablation (FLA), high-intensity focused ultrasound (HIFU), or cryoablation who had post-treatment mpMRI imaging and prostate biopsy were included in the study. The mpMRIs were evaluated and assigned a PI-FAB score (range, 1-3) by one genitourinary radiologist with 16 years of experience in PCa imaging. A total of 39 patients were included in the study, of which 30 patients underwent FLA, 6 patients underwent HIFU, and 3 patients underwent cryoablation. PI-FAB scores were correlated with MRI/TRUS fusion-guided and systematic prostate biopsies. A confusion matrix was constructed using confirmed csPCa predicted by PI-FAB scores of 3. Key performance metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess the diagnostic accuracy of the PI-FAB score. Results: Among the 39 patients included in this study, the distribution of PI-FAB scores was as follows: 16 (41.0%) scored as PI-FAB 1, 1 (2.6%) as PI-FAB 2, and 22 (56.4%) as PI-FAB 3. Eighteen (46.2%) patients had pathologically confirmed csPCa. An additional 5 patients had Gleason grade group 1 disease, bringing the total number of PCa cases to 23 (59%). Utilizing a cutoff score of PI-FAB 3 for the identification of csPCa yielded a sensitivity of 77.8% (14/18), specificity of 61.9% (13/21), PPV of 63.6% (14/22), NPV of 76.5% (13/17), and accuracy of 69.2% (27/39). The PI-FAB scoring system missed four cases of csPCa in our cohort, equating to a false negative rate of 22.2% (4/18). Conclusions: The new PI-FAB scoring system demonstrates potential as a standardized evaluation of mpMRI. Its moderately high sensitivity can be useful for stratifying patients who may benefit from subsequent prostate biopsy, but PI-FAB should be further validated in larger cohorts to better understand its utility and potential.