Based on the Miedema’s model, the formation enthalpies of Al3X(Sc, Er, Zr, Li) intermetallics were investigated. Combining with the formation theories of point defects, the formation enthalpies of mono-vacancy and anti-site defect of Al3X intermetallics were also calculated. The results show that the formation enthalpies of Al-Sc system are similar to those of Al-Er system. It indicates that scandium has the similar metallurgical chemical behavior to erbium in aluminum alloys. The mono-vacancy formation enthalpies of X atoms are all higher than those of aluminum atoms in binary compounds for Al-X(Sc, Er, Li) system, and it pointes that aluminum vacancies are formed prior to X(Sc, Er, Li) vacancies in Al-X intermetallics. The formation enthalpies of anti-site defect of Al3X intermetallics follow the sequence of Al3Er> Al3Sc > Al3Zr > Al3Li. Compared with the formation enthalpies of vacancy and anti-site defect of Al3X intermetallics, it is found that the major point defects in Al3Sc, Al3Er and Al3Zr intermetallics are the vacancy and anti-site defect while the major point defect in Al3Li intermetallic is the anti-site defect