We report a case demonstrating a late increase in acetaminophen concentration after ingestion of Tylenol Extended Relief (extended-release acetaminophen; McNeil Consumer Products) along with drugs known to slow gastrointestinal motility. Coingestants that slow gastrointestinal motility are known to affect the interpretation of serum drug concentrations. However, this case illustrates potentially significant differences between extended-release and immediate-release acetaminophen and demonstrates an exception to the current manufacturer recommendation for the use of the Rumack-Matthew nomogram in this setting.