Background: ¹⁸F-DCFPyL recently gained FDA approval for the staging of biochemically recurrent prostate cancer (PCa). After ¹⁸F-DCFPyL became available at our NCI-Designated Comprehensive Cancer Center, 164 PCa pts underwent imaging by 5/2022. Given its novelty, the clinical utility of ¹⁸F-DCFPyL versus conventional imaging (CI) is not well-defined. We evaluated the concordance and treatment impact of ¹⁸F-DCFPyL compared to CI in suspected first biochemical recurrence (BCR) and upstaging rates of ¹⁸F-DCFPyL in initial staging. Methods: The electronic medical record was queried to identify ¹⁸F-DCFPyL scans performed at our center. We selected patients (pts) with PSA recurrence after definitive frontline therapy or those undergoing initial staging. CI was within 3 months of ¹⁸F-DCFPyL. Concordance between CI and ¹⁸F-DCFPyL was assessed, with probable disease defined through assessments by the radiologist and treating oncologist and the clinical setting. Provider notes were used to capture anticipated treatment plans before and after ¹⁸F-DCFPyL. Results: For suspected BCR 30 pts had CI and 6 had two types of CI. The majority (n = 20) were MRIs of the prostate/pelvis. The remainder were nuclear bone scans (n = 4), body CTs (n = 4), ¹⁸F-fluciclovine scans (n = 3), FDG-PET (n = 1), and spinal imaging (n = 3). Discordant findings were present for 12/30 patients in shared imaging fields, of which 7 had likely disease captured solely on ¹⁸F-DCFPyL, 1 instance of disease missed on ¹⁸F-DCFPyL, and 4 instances where findings of uncertain malignant potential on CI were not tracer-avid on ¹⁸F-DCFPyL. The missed disease on ¹⁸F-DCFPyL was a PIRADS 4 prostate lesion captured on MRI. In this group, 4 cases of pelvic nodal lesions were identified on ¹⁸F-DCFPyL and not MRI. ¹⁸F-DCFPyL influenced treatment plans in 4/30 cases. Therapy was selected as follows: local salvage radiation (RT) was chosen after rule-out of systemic disease, RT was restricted to the prostate bed after a culprit lesion was found, and observation was chosen (n = 2) after disease was ruled out on PSMA-PET. For initial staging, 15 pts were thought to have prostate-only disease. On ¹⁸F-DCFPyL, 3/15 were upstaged to distant metastatic disease and 2/15 were upstaged to pelvic nodal disease. Three pts were thought to have extra-prostatic pelvic disease, of which 1/3 were upstaged to distant metastatic disease on ¹⁸F-DCFPyL. Conclusions: In the BCR setting, in which disease is often low volume, ¹⁸F-DCFPyL frequently adds valuable guidance. In our cohort ¹⁸F-DCFPyL captured additional pelvic nodal disease and helped clarify equivocal imaging, limiting unnecessary treatment. For initial staging, the 33% of pts upstaged is substantial, and further data will show whether subsequent changes in management affect outcomes. Limitations include inability to verify disease histologically and to forecast treatment decisions if PSMA-PET were not available.