Chiral discrimination effects in the monolayer of 1-O-hexadecyl glycerol (3-hexadecyl-oxy-propane-1,2-diol) amphiphile are theoretically investigated on the basis of a detailed coarse-grained molecular model. The theory uses experimentally obtained information for the average tilt and azimuthal orientation of a reference molecule and minimizes the energy of neighboring molecules using a theoretical framework developed previously. On the basis of the effective pair potential (EPP) of a neighboring pair of molecules, the mutual orientation at the minimum of EPP is obtained. The predicted curvature of the domains composed of enantiomeric amphiphiles based on the mutual orientation obtained from the EPP theory agrees with the experimentally observed handedness based on results from optical studies such as Brewster angle microscopy and fluorescence microscopy. The study revealed, for the first time, interesting crossover from heterochiral preference to homochiral preference of hexadecyl glycerol amphiphile. The theoretical result is consistent with the experimentally observed discrimination effects based on optical studies. The pair potential profiles of enantiomeric and racemic monolayers have similar features. However, the detailed distance and orientation dependences are different for enantiomeric and racemic pairs as revealed by the calculation of discrimination energy. Significant orientation dependence of chiral discrimination is observed which indicates that discrimination effects are not only dependent on intermolecular separation but also on their mutual orientation. The present study also indicates that the calculation of the magnitude of discrimination depends on the representation of molecular structure used in theoretical calculations and is consistent with our previous studies of different amphiphilic monolayers.