Abstract Purpose To compare the oncological and surgical outcomes of patients with recurrent prostate cancer (PCa) who underwent either open or newly established robot-assisted salvage prostate-specific membrane antigen–radioguided surgery (PSMA-RGS). Materials and methods Patients who consecutively underwent PSMA-RGS for PCa recurrence between January 2021 and December 2022 were identified. The rate of complete biochemical response, biochemical recurrence-free survival [BFS], and the rate of salvage therapy were evaluated. Univariable and multivariable regression models tested the association between the surgical approach and surgical outcomes. Results Overall, 85 patients were selected, with 61 patients (72%) undergoing open PSMA-RGS and 24 patients (28%) receiving a robot-assisted approach. The oncological outcomes of the two groups were comparable (12-month BFS: 41% (Confidence interval (CI): 29–58%) vs. 39% (CI: 19–79%), p = 0.9, respectively). According to multivariable regression models, the robotic approach did not significantly influence estimated blood loss (EBL) (β = −40, 95% CI: −103, 22; p = 0.2) and significantly increased operative time (OT) (β = 28, 95% CI: 10, 46; p = 0.002). No Clavien-Dindo III–V complications were reported in the robotic group. Conclusion Both, the open as well as the robot-assisted approach for PSMA-RGS had comparable oncological outcomes. No safety concerns arose for the robotic-assisted approach offering a potentially improved quality of life for patients.