In their recent study, Tsai et al1 evaluated a possible association between proton pump inhibitor (PPI) use and the development of hepatic encephalopathy (HE) in patients with cirrhosis. This is the second report of which we are aware that has examined this possible association. The first was a retrospective study by Dam et al2 that derived its population cohort from 3 separate clinical trials that were not designed to evaluate an association between PPI use and HE. They reported a hazard ratio of 1.36 (95% confidence interval, 1.01–1.84) after adjusting for multiple factors, all of which were significantly associated with HE, and also noted that only 66% of their patients had a valid indication for PPI use.