Are proton pump inhibitors (PPIs) associated with excess risk of mortality? That is the finding of a highly publicized study. Among the most popular medications worldwide, PPIs are available by prescription and over the counter. Known side effects include stroke, cardiovascular disease, interstitial nephritis, chronic kidney disease, osteoporosis, pneumonia, Clostridium difficile infections, and dementia. Researchers set out to look at whether PPIs also affect all-cause mortality. Using the Veterans Administration database, PPI users were compared to histamine 2 (H2) blocker users in a longitudinal, observational cohort study. Additional cohorts included PPI vs. no PPI, and PPI vs. no PPI and no H2 blocker. The cohorts were followed for almost six years. PPI use was associated with a 25% increased risk of death compared with H2 blockers use (adjusted hazard ratio [HR], 1.25; confidence interval [CI], 1.23-1.28). The risk also was higher when comparing PPI use to no PPI use (HR, 1.15; CI, 1.14-1.15) and PPI use to no PPI and no H2 blockers (HR, 1.23; CI, 1.22-1.24). Even factoring patients with gastrointestinal conditions, PPIs still increased the risk compared to H2 blockers (HR, 1.24; CI, 1.21-1.27). Among new PPI users, there was an increased risk of death with longer duration of treatment. The authors concluded that there is an excess risk of death among PPI users and that “limiting PPI use and duration to instances where it is medically indicated may be warranted.” Although these findings sound ominous, the absolute change in death rate was small. (BMJ Open 2017 July 4;7:e015735. doi: 10.1136/bmjopen-2016-015735)