Objectives: The objective was to ascertain whether acetaminophen (APAP) concentrations less than 100 lg/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 lg/mL drawn between 1 and 4 hours after acute ingestions, and concentrations drawn 4 or more hours after ingestions, were included in the study. Exclusion criteria included initial concentration >100 lg/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 lg/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 <100 lg/mL between 1 and 4 hours, one patient (1.2%) had a ≥ 4-hour toxic concentration. Negative predictive value (NPV) for an APAP concentration <100 lg/mL obtained between 1 and 4 hours after an acute ingestion was 98.8% (95% confidence interval [CI] = 93.5% to 99.8%).Conclusions: An APAP concentration of <100 lg/mL obtained between 1 and 4 hours after ingestion has a high NPV for excluding toxic ingestion. We do not recommend reliance on concentrations obtained between 1 and 4 hours to exclude toxicity, because of a potential false-negative rate of 6.5%.ACADEMIC EMERGENCY MEDICINE 2013; 20:1072-1075 © 2013 by the Society for Academic Emergency Medicine T here are approximately 50,000 patients who present to emergency departments (EDs) each year due to acetaminophen (APAP) exposure. 1 Those patients with acute ingestions are risk stratified by plotting their APAP concentrations on the RumackMatthew nomogram. 2 The nomogram is only validated for concentrations drawn 4 hours or later after acute APAP ingestions. The 4-hour starting point was chosen because of the initial available data at the time the nomogram was developed and to include the possibility of delayed absorption. 2 However, based on therapeutic dose pharmacokinetics, APAP concentrations should peak much earlier (within 1 hour), 3 suggesting that earlier concentrations may be predictive of toxicity.From the