Objectives The objective was to ascertain whether acetaminophen (APAP) concentrations less than 100 μg/mL obtained between 1 and 4 hours after acute ingestion accurately predict a nontoxic 4-hour concentration. Methods The authors performed a multicenter, prospective cohort study involving five emergency departments (EDs) participating in the ToxIC Research Network. Data were collected from May 2009 to December 2011. Patients with APAP concentrations 100 μg/mL, initial APAP concentration drawn prior to 1 hour, two undetectable APAP concentrations, the second concentration drawn prior to 4 hours, and unknown time of ingestion. Toxic concentrations 4 or more hours after ingestion were defined as concentrations that plotted above the 150 μg/mL line on the Rumack-Matthew nomogram. Results Data were collected on 83 patients who met inclusion criteria. Of the 83 patients with APAP concentrations