GOALS: To assess the feasibility and safety of endoscopic ultrasound-guided laser ablation (EUS-LA) of retroperitoneal lymph node (RPLN) metastasis. BACKGROUND: RPLN metastasis is challenging to treat, partly due to hazardous location. EUS-LA is a new attractive option for lesions in high-risk or percutaneous difficult-to-reach locations. Here, we reported the initial experience with EUS-LA of RPLN metastases. STUDY: From November 2016 through July 2023, patients with oligometastatic RPLN metastases who were not eligible or refused surgery were prospectively enrolled. EUS-LA was performed using a neodymium: yttrium-aluminum-garnet (Nd: YAG) laser beam fiber ablation system. The technical success rate, focal control rate, visual analog scale (VAS) scores, and adverse events were assessed. RESULTS: Nineteen patients with 25 RPLN metastases were included in the study. EUS-LA was performed successfully in all patients. The 3-month, 6-month, and 12-month focal control rates were 96.0%, 86.4%, and 76.5%, respectively. During a median follow-up of 24 months (3 to 46 mo), the median diameter of the RPLN metastases changed from 22 mm (12 to 44 mm) at baseline to 8.5 mm (6 to 39 mm) at the final follow-up. After ablation, the VAS scores decreased significantly in all patients with pain. Two patients experienced self-limited abdominal pain, and no moderate or severe adverse events were reported. CONCLUSIONS: EUS-LA showed high technical feasibility and an acceptable safety profile in the treatment of oligometastatic RPLN metastases. In patients at high surgical risk, EUS-LA can be considered as an alternative therapeutic modality, which warrants a long-term follow-up study to verify the efficacy.