Differential complexation of fenoprofen enantiomers by cyclomaltoheptaose (beta-cyclodextrin) was investigated by Monte Carlo docking simulations. The chiral discrimination of (R)- and (S)-fenoprofen by beta-cyclodextrin was discussed in terms of the difference in the interaction energies and the patterns of molecular interactions. The interaction energies between each enantiomer of fenoprofen and beta-cyclodextrin were consistent with the reported experimental results that showed that the S isomer interacted preferentially with beta-cyclodextrin and was retained longer in a separation process than the R isomer. The thermodynamic preference of inclusion complex formation of (S)-fenoprofen could be explained by the orientation of the phenyl group attached to the chiral carbon, which provided closer contact and thus more favorable intermolecular interactions between the host and guest molecule. The results presented here would be very useful for the prediction of chiral recognition ability of beta-cyclodextrin.