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New-onset seizures (NOS) are a common reason for emergency department (ED) consultations. Decisions regarding treatment and further examinations are made based on the initial evaluation. We aimed to evaluate the reliability of the early syndromic diagnosis in NOS and find predictive factors to establish a consistent early diagnosis based on the semiology and prompt supplementary examinations.We recruited patients attended in our ED for NOS over 2 years (2014-2015), excluding patients with a loss of consciousness of suspected non-epileptic origin. All patients were assessed by a neurologist. A baseline diagnosis was established according to clinical findings and neuroimaging/EEG data. Over 1 year of follow-up in our Epilepsy Unit, a definite diagnosis was made based on clinical progress and further examinations.116 patients were recruited (mean age 56.5 ± 22.1 years; 50% women). 47% were seizures of unknown cause. The concordance index between the baseline and definite diagnosis was κ = 0.662 (the diagnosis changed during follow-up in 25% of patients). Focal epilepsy of unknown cause was the baseline diagnosis that most often changed at follow-up (diagnostic change, 41.2%; p 0.001). Lesions detected on CT-scanning and EEG abnormalities predicted the final diagnosis with the greatest accuracy (p = 0.009 and p = 0.026, respectively). Pathological findings in the MRI studies performed and seizure recurrence were not key factors for diagnostic changes.Despite prompt examinations, the baseline epilepsy diagnosis changes within a short time period in 25% of patients. The presence of neuroimaging lesions and EEG abnormalities was associated with the greatest diagnostic accuracy in these cases.