The aim of this study was to compare the efficacy of the Neurological Depressive Disorders Inventory for Epilepsy (NDDI-E) and the depression component of the Hospital Anxiety Depression Scale (HADS-D) for identifying depression and suicide risk in adults with epilepsy. A total of 147 (87 female [59% ]) outpatients attending a tertiary epilepsy center in Sydney Australia completed the NDDI-E and HADS-D. They then completed the depression and suicide sections of the Mini International Neuropsychiatric Inventory (MINI) with a clinician blind to symptom measure scores. Receiver operator characteristic analysis was performed for the clinical cutoff scores for depression on the NDDI-E ≥ 15 and HADS-D ≥ 8 to identify MINI-determined depression and suicidality. The NDDI-E indicated strong sensitivity (84%) and acceptable specificity (78%), whereas the HADS-D had poor sensitivity (42%) but good specificity (97%) for identifying depression. For identifying suicide risk, the NDDI-E indicated strong sensitivity (81%) and reasonable specificity (66%), whereas the HADS-D had poor sensitivity (43%) but acceptable specificity (90%). Area under the curve comparisons for these measures were not significant. In clinical practice, it is essential that screening measures have the highest possible sensitivity values to limit the chances of false-negative results. In accordance with these guidelines, the NDDI-E was a superior screening measure compared with the HADS-D. Our results demonstrate the efficacy of the NDDI-E for identifying both major and minor depression and serious suicide risk. The poor sensitivity of the HADS-D suggests that it should not be used as a screen for depression or suicidality in adults with epilepsy.