A retrospective study in intensive-care patients found that H2 receptor antagonists were associated with lower hospital-acquired C. difficile infection risk than proton pump inhibitors (PPIs). The analysis covered 15,462 ICU patients and adds to ongoing debate around which widely used acid-suppressing therapies most affect C. difficile outcomes in vulnerable populations. Clinically, the results could influence antimicrobial stewardship and prophylaxis decisions, especially in settings where ICU patients are already at high baseline risk. While the retrospective design cannot establish causality, the signal is actionable for infection-prevention teams evaluating current protocols. For biotech stakeholders, the study’s relevance is mainly indirect—informing the real-world incidence landscape for C. difficile and shaping demand patterns for diagnostics and therapeutics in hospital-acquired infection management.