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Background: In February 2021 Medtronic® (Minneapolis, MN) launched the HUGO™ Robot-Assisted Surgery (RAS) System in the global market. The aim of the current study is to describe the first case series and the optimal setup of robot-assisted pyeloplasty procedure, performed with HUGO RAS system in a tertiary referral robotic center. Methods: Data from consecutive patients who underwent robot-assisted pyeloplasty at Onze-Lieve-Vrouwziekenhuis Hospital (Aalst, Belgium) were recorded. Baseline characteristics, and perioperative and surgical outcomes were collected. Results: Overall, 10 robot-assisted pyeloplasties were performed (October 2022–September 2023). Based on our expertise, the following minor setting changes have been made, relative to the official setup guide: the endoscope port and, subsequently, the left and right-hand ports were positioned more laterally. Additionally, the reserve/4th port was placed more laterally and cranially, and adjusted the arm cart's tilt angle, reducing it from −30° to −15°. The median docking time was 8 (interquartile range [IQR]: 7.2–9.8) minutes, and the median active console time was 89.5 (80.0–95.8) minutes. No conversion to open/laparoscopic surgery or perioperative complications was encountered. A single technical problem was recorded in 1 (10%) procedure. Specifically, one arm was blocked, and the procedure was accomplished with three arms without compromising the procedure success. Conclusions: This study represents the first worldwide series of robot-assisted pyeloplasty performed with the HUGO RAS system and shows promising results. The procedure might be safely performed with this robotic platform achieving optimal perioperative outcomes. [ABSTRACT FROM AUTHOR]