The chiral discrimination in the self-association of chiral 1,3a,4,6a-tetrahydroimidazo[4,5-d]imidazoles has been studied using density functional theory methods. Clusters from dimers to heptamers have been considered. The heterochiral dimers (RR:SS orSS:RR) are more stable than the homochiral ones (RR:RR or SS:SS) with energy differences up to 17.5 kJ/mol. Besides, in larger clusters the presence of two adjacent homochiral molecules impose an energetic penalty when compared to alternated chiral systems (RR:SS:RR:SS...). The differences in interaction energy within the dimers of the different derivatives have been analyzed based on the atomic energy partition carried out within the atoms in molecules framework. The mechanism of proton transfer in the homo- and heterochiral dimers shows large transition-state barriers except in those cases in which a third additional molecule is involved in the transfer. The optical rotatory power of several clusters of the parent compound have been calculated and rationalized based on the number of homochiral interactions and the number of monomers of each enantiomer within the complexes.