Multiple hypothesis testing (or multiple testing) refers to testing more than one hypothesis within a single analysis, and can inflate the type I error rate (false positives) within a study. The aim of this review was to quantify multiple testing in recent large clinical studies in the otolaryngology literature and to discuss strategies to address this potential problem. Original clinical research articles with >100 subjects published in 2012 in the four general otolaryngology journals with the highest Journal Citation Reports 5-year impact factors. Articles were reviewed to determine whether the authors tested greater than five hypotheses in at least one family of inferences. For the articles meeting this criterion for multiple testing, type I error rates were calculated, and statistical correction was applied to the reported results. Of the 195 original clinical research articles reviewed, 72% met the criterion for multiple testing. Within these studies, there was a mean 41% chance of a type I error and, on average, 18% of significant results were likely to be false positives. After the Bonferroni correction was applied, only 57% of significant results reported within the articles remained significant. Multiple testing is common in recent large clinical studies in otolaryngology and deserves closer attention from researchers, reviewers, and editors. Strategies for adjusting for multiple testing are discussed. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.