This diagnostic accuracy study compared the accuracy of seizure detection by amplitude-integrated electroencephalography with the criterion standard conventional video EEG in term and near-term infants at risk of seizures. Simultaneous recording of amplitude-integrated EEG (2-channel amplitude-integrated EEG with raw trace) and video EEG was done for 24 hours for each infant. Amplitude-integrated EEG was interpreted by a neonatologist; video EEG was interpreted by a neurologist independently. Thirty-five infants were included in the analysis. In the 7 infants with seizures on video EEG, there were 169 seizure episodes on video EEG, of which only 57 were identified by amplitude-integrated EEG. Amplitude-integrated EEG had a sensitivity of 33.7% for individual seizure detection. Amplitude-integrated EEG had an 86% sensitivity for detection of babies with seizures; however, it was nonspecific, in that 50% of infants with seizures detected by amplitude-integrated EEG did not have true seizures by video EEG. In conclusion, our study suggests that amplitude-integrated EEG is a poor screening tool for neonatal seizures.