Proton pump inhibitors (PPIs) have revolutionized the management of acid-related disorders. The potential adverse effects related to PPI use fall into four main categories: idiosyncratic reactions, drug-drug interactions, drug-induced reflex hypergastrinemia, and drug-induced hypochlorhydria. Clostridium difficile (C. difficile) colitis, an epidemic of major importance among hospitalized individuals, is potentially facilitated by the fourth mechanism in PPI users. This article interprets the results of the accompanying study by Aseeri et al. that demonstrated a positive association between PPI exposure and C. difficile colitis by examining the findings according to the Bradford Hill criteria. Instead of stopping PPIs when patients are admitted to hospital, I propose continuing the therapy at the lowest effective maintenance dose and adhering to careful barrier nursing and hand washing among patients.