We reported an effect of proton pump inhibitors (PPIs) leading to vascular dysfunction (Circulation 2013;128:845–853). Based on that finding, we hypothesized that PPIs may be associated with an increased risk of myocardial infarction, and reapplied a validated data-mining method to examine for the presence of a drug safety signal in electronic medical records. With regard to the critique of our paper (PLoS One 2015;10:e0124653), the commentators have attributed many of the limitations of observational studies to our data-mining study.