Abstract A synergistic effect of selective separation of (S)-amlodipine using the di(2-ethylhexyl)phosphoric acid (D2EHPA) with the tartaric acid derivatives, O,O′-dibenzoyl-(2S,3S)-tartaric acid ((+)-DBTA) was developed for the enantioseparation of racemic amlodipine. The extractants were diluted in 1-decanol with various proportions. The influences of the extractant compositions, the concentrations of amlodipine enantiomers and the extractive equilibrium temperatures were studied. The extraction and recovery of (S)-amlodipine from the feed phase in a single-module operation were 84.50% and 80.50%, respectively. The maximum percentage of enantiomeric excess of (S)-amlodipine was 70.21%. The aqueous-phase mass-transfer coefficient (kf) and organic-phase mass-transfer coefficient (km) were reported to 4.87 × 10−2 and 2.89 × 10−2 cm/s, respectively. Therefore, the mass transfer-controlling step is the diffusion of (S)-amlodipine complex through liquid membrane. The potential application of the synergistic system to separate (S)-amlodipine from pharmaceutical wastewaters has also been discussed. The results showed that synergistic extraction technique can be applied for large-scale production of the pure enantiomeric compound.