The purpose of the present study was to determine the thermodynamic stability orders of co-crystals by co-crystal former (CCF) exchange reactions. Caffeine (CA) was employed as a model drug. The CCF exchange reaction was performed by liquid-assisted grinding using ethanol. When oxalic acid (OX) was added to CA–citric acid co-crystal (CA–CI), CA–CI converted to CA–OX, suggesting that CA–OX is more stable than CA–CI. The stability orders of other co-crystals were determined in the same manner. The stability order of CA co-crystals was determined as CA–OX≈CA–p-hydroxybenzoic acid (HY)>CA–CI>CA–malonic acid>CA–maleic acid. The stability order correlated with the difference in hydrogen bond energy estimated in silico, except for CA–HY. The π–π stacking in CA–HY was suggested as a reason for this discrepancy. The CCF exchange reaction was demonstrated as a useful method to determine the stability order of co-crystals, which can be used for the validation of in silico parameters to predict co-crystal formation.