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Objectives: The objective of this study was to evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) and 68Ga prostate-specific membrane antigen positron emission tomography–computed tomography (PSMA PET-CT) and respective quantitative parameters (Ktrans – influx rate contrast, Kep – efflux rate constant, ADC – apparent diffusion coefficient, and SUVmax ratio – prostate SUVmax to background SUVmax ratio) in detection and localization of clinically significant prostate cancer (CSPCa) in D’Amico intermediate- and high-risk group patients (prostate-specific antigen [PSA] >10 ng/ml). Methodology: The study included thirty-three consecutive adult men with serum prostate specific antigen >10ng/ml, and systematic 12 core prostate biopsy proven prostate cancer. All the 33 patients, were evaluated with mpMRI, and 68Ga PSMA PET-CT. The biopsy specimens and imaging were evaluated for 12 sectors per prostate by a predetermined scheme. Results: MpMRI Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score ≥3 showed higher sensitivity than 68Ga PSMA PET-CT (96.3% vs. 82.4%), with similar specificity (54.5% vs. 54.5%) (n = 33 patients, 396 sectors). Combined use of MRI and 68Ga PSMA PET-CT in parallel increased sensitivity (99.5%) and NPV (98.7%) for detection of CSPCa and combined use of MRI and 68Ga PSMA PET-CT in series increased specificity (71.8%) and PPV (71.5%) (n = 33 patients, 396 sectors). ADC showed a strong negative correlation with Gleason score (r = −0.77), and the highest discriminative ability for detection and localization of CSPCa (area under curve [AUC]: 0.91), followed by Ktrans (r = 0.74; AUC: 0.89), PI-RADS (0.73; 0.86), SUVmax ratio (0.49; 0.74), and Kep (0.24; 0.66). Conclusion: MpMRI PI-RADS v2 score and 68Ga PSMA PET-CT (individually as well as in combination) are reliable tool for detection and localization of CSPCa. Quantitative MRI and 68Ga PSMA PET-CT parameters have potential to predict Gleason score and detect CSPCa.