Background: The local staging of prostate cancer relies on systematic or targeted biopsies and multiparametric magnetic resonance imaging (mpMRI). The role of prostate-specific membrane antigen (PSMA)-targeted PET in the evaluation of intraprostatic cancer foci and T-staging assessment is not well defined. The goal of this analysis was to compare the diagnostic performance of PSMA PET/CT, mpMRI and the combination of the two (PSMA PET/CT+mpMRI) in the detection, intra-prostatic localization and local extension of primary prostate cancer with histopathology as the gold standard.Methods: Patients with intermediate- or high-risk prostate cancer underwent a PSMA PET/CT scan and mpMRI prior to intended radical prostatectomy. Each imaging modality was interpreted by 3 blinded independent readers. A majority rule was applied (2:1). A standardized approach was used to assess presence, location and size of prostate cancer foci within the prostate. The analysis was conducted on a lesion- and segment-level. Whole mount pathology was interpreted by a Genito-Urinary pathologist using the same standardized method described above. Accuracy in determining the location, extra-capsular extension (ECE) and seminal vesicle invasion (SVI) of prostate cancer foci were assessed using receiver operating characteristic (ROC) analysis. A “raw-stringent” and “neighboring” approach were used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Results: The final analysis included 74 patients. Detection rate was 75%, 79% and 82% using the “raw-stringent” approach, 86%, 83% and 87% using the “neighboring” approach for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. Differences in detection rates between PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI were not statistically significant. The two imaging modalities performed similarly (AUC = 0.70 vs 0.73, p = 0.09; AUC = 0.77 for the two together) in localizing prostate cancer. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone was statistically significant (p < 0.001), but not between PSMA PET/CT and mpMRI (p = 0.093). mpMRI performed better than PSMA PET/CT in the T-staging assessment: ECE (AUC = 0.79 vs 0.59, p = 0.002) and SVI (AUC = 0.84 vs 0.63, p = 0.001). Conclusions: PSMA PET/CT and mpMRI have similar diagnostic accuracy in the detection and intra-prostatic localization of prostate cancer foci while mpMRI performs better in the assessment of ECE and SVI. The combination of the two imaging modalities improves performance of the two modalities alone, but this does not reach statistically significant levels on a lesion-level and might not justify changes in the current practices for local staging of prostate cancer.