Purpose: The purpose of this study was to determine whether hepatotoxicity could be predicted early using biochemical markers in patients with acetaminophen (AAP) poisoning and to assess the usefulness of predictive factors for acute liver injury or hepatotoxicity. Methods: This study was a retrospective observational study involving a medical records review. The participants were patients who were admitted to the emergency department (ED) with AAP overdose at two hospitals over a 10-year period. Demographic data, age, time from ingestion to visit, initial AAP level, initial hepatic aminotransferases, and initial prothrombin time were recorded. Acute liver injury was defined as a peak serum ALT >50 U/L or double the admission value, and hepatotoxicity was defined as a peak ALT >1,000 U/L. Receiver operating characteristic curve analyses were performed to compare the prognostic performance among variables. Results: A total of 97 patients were admitted to the ED with AAP overdose, of whom 26 had acute liver injury and 6 had hepatotoxicity. Acute liver injury was associated with the time interval after taking the drug, and hepatotoxicity was associated with the initial PT and the ALT level. The scoring system proposed by the authors has a significant ability to predict both acute liver injury and hepatotoxicity. Conclusion: To predict the prognosis of AAP poisoning patients, the time interval after taking AAP was important, and initial prothrombin time and ALT level were useful tests. Also a scoring system combining variables may be useful.