Objectives: To investigate the diagnostic capability of anterior temporal lobe white matter abnormal signal (ATLAS) for determining seizure focus laterality in temporal lobe epilepsy (TLE) by comparing different MR sequences. Methods: This prospective study was approved by the institutional review board and written informed consent was obtained. Three 3D sequences (double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging (T2WI)) and two 2D sequences (FLAIR and T2WI) were acquired at 3T. Signal changes in the anterior temporal white matter of 21 normal volunteers were evaluated. ATLAS laterality was evaluated in 21 TLE patients. Agreement of independent evaluations by two neuroradiologists was assessed using κ statistics. Differences in concordance between ATLAS laterality and clinically defined seizure focus laterality were analysed using McNemar's test with multiple comparisons. Results: Pre-amygdala high signals (PAHS) were detected in all volunteers only on 3D-DIR. Inter-evaluator agreement was moderate to almost perfect for each sequence. Correct diagnosis of seizure laterality was significantly more frequent on 3D-DIR than on any other sequences (P ≤ 0.031 for each evaluator). Conclusions: The most sensitive sequence for detecting ATLAS laterality was 3D-DIR. ATLAS laterality on 3D-DIR can be a good indicator for determining seizure focus localization in TLE. Key Points: • Magnetic resonance imaging is widely used to investigate temporal lobe epilepsy. • Numerous MR sequences can show anterior temporal lobe white matter abnormal signal. • ATLAS on 3D-DIR can frequently indicate seizure focus laterality in TLE. • 3D-DIR is more sensitive about ATLAS laterality than T2WI or FLAIR. © 2012 European Society of Radiology.