Background <p>Treatment options for malignant loculated pericardial effusions are limited and effusions often reaccumulate following surgical management. For posterior effusions, access percutaneously is challenging, hence alternative approaches may be needed. Here, we report a rare case of transoesophageal endoscopic ultrasound (EUS)-guided pericardiocentesis for recurrent loculated posterior malignant pericardial effusion causing haemodynamic compromise.</p> Case presentation <p>A 65-year-old male was diagnosed with metastatic lung adenocarcinoma following an emergency admission with malignant cardiac tamponade. He underwent percutaneous pericardiocentesis under transthoracic ultrasound guidance and was started on osimertinib for an EGFR-exon-19 sensitising mutation. 6 weeks later, he was readmitted with symptomatic pericardial effusion and underwent an urgent pericardial window. The procedure was complicated due to multiple loculations, densely adherent sac, and poor respiratory reserve. Re-staging CT scan at the time showed partial response to osimertinib.</p> <p>Two weeks post-discharge, repeat echocardiography showed a 4.0 cm loculated posterior pericardial effusion compressing the left atrium, with evidence of haemodynamic compromise. Further percutaneous drainage was not feasible due to the posterior location, and his anaesthetic risk for repeat thoracotomy was considered prohibitively high. Due to his good pre-morbid baseline, favourable genomic profile, and ongoing response to osimertinib, the multidisciplinary team trialled an unconventional approach using transoesophageal pericardiocentesis under endoscopic ultrasound (EUS) guidance under conscious sedation. The procedure was uncomplicated and 100mL of haemosanguinous fluid was drained with immediate symptomatic relief. Pericardial cytology was negative for malignant cells and extended pericardial culture grew Klebsiella, a contaminant from the gastrointestinal tract. The effusion reaccumulated four weeks later and restaging CT eight weeks post-drainage suggested early progressive disease. The patient further deteriorated and passed away, six months from his initial presentation with malignant pericardial tamponade.</p> Conclusion <p>We present one of few reported cases of successful transoesophageal EUS-guided pericardiocentesis as a potential alternative for pericardial effusion drainage. Improved prognosis in patients with metastatic lung cancer, especially those with actionable genomic aberrations, should be considered for more aggressive therapeutic approaches when no other alternatives exist following clear discussion regarding risks and benefits.</p>