EUS-guided gallbladder drainage (EUS-GBD) is emerging as a valuable treatment for acute cholecystitis (AC) in patients unfit for surgery. When lumen-apposing metal stents are used, large-caliber access to the gallbladder allows for subsequent direct peroral endoscopic cholecystoscopy (POEC) and eventual cholecystolithotomy (CL), offering a potentially "curative" solution for frailer patients. The aim of this series was to evaluate the outcome of these procedures in oncologic patients experiencing AC, with a specific focus on chemotherapy continuity.A prospective registry of all consecutive therapeutic EUS procedures performed in the San Raffaele Institute between December 2020 and April 2021 was searched for EUS-GBD + POEC-CL performed in chemotherapy candidates. Clinical and technical variables were prospectively registered, as were days of chemotherapy delay and postprocedural outcomes.Three consecutive patients with a diagnosis of a malignancy (2 pancreatic cancers and 1 severe myeloproliferative disease with skeletal lesions) experienced AC and were primarily treated by EUS-GBD. After 4 weeks, they were systematically scheduled for POEC-CL and lumen-apposing metal stent exchange for a double-pigtail plastic stent. All procedures and revisions were successful, with rapid clinical improvement. All gallbladders were cleared of food debris and stones between 3 and 15 mm using grasping forceps, polypectomy snares, Dormia baskets, and mechanical lithotripsy. One mild adverse event without any clinical consequence was registered during POEC-CL. Revisions did not interfere with the chemotherapy schedule. Technical variables (eg, gastric vs duodenal drainage or need for coaxial double-pigtail plastic stent) are discussed.EUS-GBD and subsequent POEC-CL allows a highly effective and minimally invasive solution for AC. These initial experiences promote further evaluation of this approach for all those individuals in whom surgical interventions are undesirable, such as oncologic patients whose prognosis depends on chemotherapy continuity, although further prospective confirmation in this setting should be pursued.