Study aim: Compare pantoprazole vs vonoprazan for stress bleeding prophylaxis in ICU. Design: Parallel two-arm RCT, blocks 4&6, 1:1 allocation, opaque numbered envelopes. Double-blinded (patients, staff, analyst blinded). Drugs identically packaged by pharmacy. Settings and conduct: The intensive care unit of Imam Reza Hospital in Kermanshah. Patients are screened daily; after obtaining informed consent, randomization and drug administration by the nurse are performed. Daily monitoring for bleeding, hemodynamic changes, transfusion needs, and other outcomes is recorded by a trained researcher on pre‑designed checklists. Participants/Inclusion and exclusion criteria: Age above 18 years; admission to the intensive care unit with anticipated stay beyond 48 hours; need for stress ulcer prophylaxis according to the American Society of Health‑System Pharmacists or the Society of Critical Care Medicine guidelines, defined as having at least one major risk factor including mechanical ventilation beyond 48 hours, or coagulopathy with an international normalized ratio above 1.5 or platelet count below fifty thousand per mm³, or having at least two minor risk factors including sepsis, shock, acute renal failure, liver failure, severe burns, trauma or severe central nervous system injury, or high‑dose corticosteroid use equivalent to more than 250 milligrams of hydrocortisone daily. Intervention groups: Pantoprazole: 40mg IV daily until discharge, full feeding, bleeding or 14d. Vonoprazan: 20mg oral via NG tube same duration. Main outcome variables: Occurrence of clinically important gastrointestinal bleeding during intensive care unit stay; Occurrence of overt gastrointestinal bleeding without hemodynamic compromise; ventilator‑associated pneumonia; Clostridioides difficile infection; length of intensive care unit stay; 28‑day mortality.