© 2020 Hernández-Ronquillo, Thorpe, Dash, Hussein, Hunter, Waterhouse, Laboni Roy and Téllez-Zenteno. Background: The DX-Seizure study aims to evaluate the diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio) of the ambulatory EEG in comparison with the first routine EEG, and a second routine EEG right before the ambulatory EEG, on adult patients with first single unprovoked seizure (FSUS) and define the utility of ambulatory EEG in forecasting seizure recurrence in these patients after 1-year follow-up. Methods: The DX-Seizure study is a prospective cohort of 113 adult patients (≥18-yearold) presenting with FSUS to the Single Seizure Clinic for evaluation. These patients will be assessed by a neurologist/epileptologist with the first routine EEG (referral EEG) and undergo a second routine EEG and ambulatory EEG. The three EEG (first routine EEG as gold standard) will be compared and evaluated their diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) with respect of epileptiform activity and other abnormalities. One-year follow-up of each patient will be used to assess recurrence of seizures after a FSUS and the utility of the ambulatory EEG to forecast these recurrences. Discussion: To the best of our knowledge, this will be the first study to prospectively examine the use of ambulatory EEG for a FSUS in adults and its use for prediction of recurrence of seizures. The overarching goal is to improve diagnostic accuracy with the use of ambulatory EEG in patients with their FSUS. We anticipate that this will decrease incorrect or uncertain diagnoses with resulting psychological and financial cost to the patient. We also anticipate that an improved method to predicting the recurrence of seizures will reduce the chances of repeated seizures and their consequences.