Amlodipine is a widely used medication in treating hypertension, which is also known as a chiral compound. So far efforts have been made to obtain optically pure (S)-amlodipine because (R)-amlodipine has poor efficacy and is related to undesirable side effects. However, the available separation methods for amlodipine are still unsatisfactory. Recently, chiral separation has become a promising application of chiral ionic liquids (CILs), because the structural designability enables them adjustable separation efficiency for specific tasks. In this work, a high-efficient CIL-based liquid-liquid extraction system was developed for racemic amlodipine separation with the assistance of quantum chemistry calculations. Enantioselectivity up to 1.35 achieved by the novel system at 298.15 K is significantly higher than other available extraction systems. Moreover, the recycling of CIL can be easily realized by backward extraction of amlodipine, which is important for the industrial application of CILs. (C) 2018 American Institute of Chemical Engineers