The 2019 Briganti nomogram was developed to calculate the risk of lymph node invasion (LNI) and identify prostate cancer (PCa) patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy who should be considered for an extended pelvic lymph node dissection (ePLND). Since its implementation is still limited by lack of a formal external validation, we aimed to validate this tool in a large contemporary cohort. We identified 487 patients diagnosed using MRI-targeted with concomitant systematic biopsy who underwent radical prostatectomy (RP) and an anatomically defined ePLND at six centers. The external validity of the 2019 Briganti nomogram for estimating LNI risk was assessed via calibration, discrimination, and decision curve analyses (DCAs). A total of 38 (8%) patients had LNI at final pathology. The median number of nodes removed was 18 (interquartile range 14-24). On external validation, the 2019 Briganti nomogram had an area under the receiver operating characteristic curve (AUC) of 79%. Although there was some miscalibration, this was at predicted probabilities >35% and therefore outside the clinically relevant range. DCA demonstrated that the 2019 Briganti nomogram improved clinical risk prediction against LNI threshold probabilities of ≤30%. For a 7% cutoff, 273 (56%) ePLNDs would be spared and only 2.6% LNIs would be missed. The 2019 Briganti nomogram was characterized by higher AUC compared to the 2012 and 2017 Briganti nomograms and the Memorial Sloan Kettering Cancer Center risk calculator (79% vs 75% vs 65% vs 74%) and demonstrated the highest net benefit on DCA. This first multi-institutional validation of the 2019 Briganti nomogram in predicting LNI in PCa patients diagnosed with MRI-targeted biopsy confirms the highest AUC, better calibration and the highest net benefit compared with available tools and should be adopted to identify candidates for ePLND among men diagnosed with MRI-targeted biopsy. PATIENT SUMMARY: We performed the first multi-institutional validation of the first nomogram predicting lymph node invasion specifically developed using data from prostate cancer patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. This nomogram exhibited excellent characteristics on external validation compared with available tools and should be adopted to identify candidates for extended pelvic lymph node dissection among men diagnosed with MRI-targeted biopsy.