To the Editor Maggio and colleagues demonstrated a 51% increased 1-year mortality with the use of proton pump inhibitors (PPIs) in elderly patients discharged from acute care hospitals.1 However, a meta-analysis of 20 randomized clinical trials did not show a difference in all-cause mortality (odds ratio, 1.01; 95% CI, 0.74-1.40) between the use of PPIs (n = 2020) and the use of placebo or histamine 2 receptor antagonists (n = 2062).2 Observational studies show harmful effects of PPIs on various health outcomes surprisingly often, whereas randomized clinical trials do not. For example, observational studies showed a 34% increased risk of major adverse cardiac events following PPI use vs nonuse,3 which was not confirmed in randomized clinical trials (rate ratio, 0.99; 95% CI, 0.68-1.44) (median age of 69 years).4 The discrepancy between randomized trials and observational studies may be explained by residual confounding in epidemiological studies. Individuals taking PPIs often have a higher disease burden, which is not fully accounted for. Additional examples include an excessive alcohol intake, a sedentary lifestyle, and the use of systemic corticosteroids,5 which was not adjusted for in the observational study by Maggio and coworkers.1