Background: The decision to treat an acute acetaminophen overdose patient is based on plotting the acetaminophen concentration on the Rumack-Matthew nomogram. In 2012, the UK’s Medicines and Healthcare Products Regulatory Agency lowered the treatment threshold by 50 %, mandating treatment if a 4-h acetaminophen concentration exceeded 100 mcg/mL. Hypothesis: We hypothesize the number of additional patients who would require treatment for acetaminophen ingestions can be estimated using data from a diverse group of hospital Emergency Departments (EDs). Methods: In this institutional review board-approved study, patients >13 years who presented to one of seven US hospitals with an acute acetaminophen ingestion between 7/1/2008 and 6/30/2013 were screened. Patients who would require treatment based on the current (revised) UK nomogram, but not the current US nomogram, were included. The estimated number of cases nationally was extrapolated by taking the proportions of cases at each hospital as a percentage of total ED visits for that center and applying this to the total number of annual ED visits in that participating county and then to the US. County and national visit information was obtained from the Area Health Resources Files from the Department of Health and Human Services. Results: One hundred seven eligible patients were identified. The median age was 23 (18–35) years; 63 % were female. Applying the revised UK nomogram to the US population would result in treating an additional 5.4 cases/100,000 patients. Extrapolating this number nationally, an estimated 6,951 (95 % CI 0–24,585) additional patients would be treated annually. Discussion: Patients whose acetaminophen concentration falls below the currently used US nomogram historically have a very low rate of developing hepatic failure. Adapting the current UK treatment strategy in the US would increase the number of patients treated (and exposed to potential iatrogenic complications) and increase costs without providing any likely clinical benefit. Conclusion: Adopting the revised UK treatment threshold to acute APAP ingestions in the US would result in treating an additional 6,951 patients annually.