Introduction: Bupropion is a popular antidepressant due to its favorable side effect profile and indications for smoking cessation and weight loss. Due to the possibility of delayed onset seizure and other adverse outcomes after bupropion overdose, patients are often observed for periods of 12-24 hours following suspected ingestion. Tachycardia is a clinical predictor that holds promise in differentiating cases at risk for seizures from low-risk cases that do not require prolonged observation. This study assessed whether heart rate within the first eight hours of presentation can identify cases that do not require extended observation., Methods: This is a retrospective cohort study of all supra-therapeutic bupropion cases from two hospital systems between 2010 and 2022., Results: Data from 216 charts were included. Seizures, hypotension, and dysrhythmias occurred in 19 percent ( n = 41), 1.4 percent ( n = 3), 0.9 percent ( n = 2) respectively. One patient died. Delayed adverse effects were rare ( n = 4); they occurred from 14 hours to 28 hours post-ingestion. Maximum heart rate in eight hours was associated with a risk of adverse outcomes. (odds ratio, 1.07; 95 percent confidence interval: 1.05 to 1.09; P < 0.001). An eight hour maximum heart rate threshold of 104 beats/minute had a negative predictive value of 100 percent (95 percent confidence interval: 96.7 percent to 100 percent) for the occurrence of delayed adverse effects. All patients with delayed effects had tachycardia within five hours of emergency department arrival., Discussion: Delayed adverse outcomes of seizures, hypotension, dysrhythmia, and death were uncommon in this cohort. Heart rate during the first eight hours of observation performs reliably as a screening test to identify patients at low risk for delayed adverse outcomes. This study is limited by its retrospective nature, the inability to ascertain time of ingestion for most cases and the lack of confirmatory laboratory testing., Conclusion: This study supports the use of an eight hour observation period when there are no other clinical signs of toxicity to warrant admission and if no co-ingestion or administration of substances that mask tachycardia are present.