Introduction <p>The rate of false-negative results for Transrectal Ultrasound-guided prostate (TRUS-TB) biopsy for clinically suspicious carcinoma prostate (CaP) may be as high as 35% depending on used techniques. The objective of this study was to determine the diagnostic yield of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy (PSMA PET-TB) in suspected carcinoma prostate cases with negative TRUS-guided biopsy.</p> Methods <p>Those cases with high clinical suspicion of CaP with a benign histopathology report following TRUS-TB over a period of 23&#xa0;months were evaluated using 68&#xa0;Ga-PSMA PET/CT scan to localize the avid lesion, and PSMA PET-TB was done. Data available from mpMRI studies done during the time of diagnosis were also used. Concordance was calculated for different sites by method of Kappa for test of agreement between 2 modalities, in addition to calculation of various screening test parameters using ROC curves.</p> Results <p>The mean PSA of the cohort (ng/mL) was 20.34 ± 23.90 (95% CI 14.48, 28.20). Of the 50 patients who were negative on TRUS-TB but showed a PSMA-avid lesion, 43 were included; of these, 39 were diagnosed with prostate cancer (CaP), and 20 had a Gleason score of 3&#xa0;+&#xa0;3 (Grade Group 1). The sensitivity, specificity, and diagnostic yield of PSMA PET scan were 84.62, 75, and 97.06%, respectively, at an SUVmax &gt; 6.95 on ⁶⁸&#xa0;Ga-PSMA scan. 37 out of the 39 CaP cases with anteriorly located lesions missed on TRUS-TB were accurately targeted and diagnosed by PSMA PET-TB. 33 cases with PIRADS score &gt; 3 and SUVmax &gt; 6.95 were diagnosed as CaP by PSMA PET-TB in cases negative on TRUS-TB.</p> Conclusions <p>PSMA PET-TB is a valuable tool to diagnose clinically suspicious prostate cancer in patients with initially negative TRUS-TB.</p>