Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS.