Noninferiority (NI) trials aim to show that a new treatment or drug is not inferior to a standard, accepted treatment. The rapid proliferation of NI trials within the literature makes it imperative for emergency physicians to be able to read, interpret, and appraise critically this type of research study. Using several emergency medicine examples from the recent literature, this article outlines the key differences between traditional, superiority randomized controlled trials and NI trials. We summarize four important points that an emergency physician should consider when critically appraising an NI trial: 1) Does the new treatment have tangible benefits over the standard treatment? 2) Was the choice of the NI margin appropriate? 3) Was the effect of the standard treatment preserved? Does the trial have assay sensitivity? and 4) What type of analysis strategy was employed: intention-to-treat (ITT) or per protocol (PP)?