This research was aimed to study effect of molecular size on the activity coefficient of glycols in aqueous solution. The studied glycols were ethylene glycol, 1,2-propylene glycol, and 1,4-butylene glycol. A vapor liquid equilibrium still was designed and used to produce isothermal VLE experimental data for 1.4-butylene glycol-water at temperature of 98, 110, and 122 ํC, which cover the optimal temperature range for the distillation process of glycols in water. By fitting experimental VLE data of 1,4-butylene glycol in water with UNIQUAC or Wilson model with the aid of computer programming, the activity coefficient was obtained. The estimated activity coefficient of 1,4-butylene glycol in water was compared with that of literature results of ethylene glycol and 1,2-propylene glycol in water to study the effect molecular size. The results shown that the UNIQUAC and Wilson models are capable of estimating with good accuracy the equilibrium conditions for such mixture. The activity coefficient of each system depends on temperature and composition. The activity coefficient also depends on molecular size and shape of glycols in aqueous solution. The activity coefficient of straight chain glycols trend to decrease when the molecular size is increased and that value of the branch chain glycol is greater than of the straight chain. The effect of molecular size together with molecular structure may be explained by interaction of component, which can be presented by boiling point of component. However, the effect of molecular size of glycols in water can be more significantly presented by the parameters of both UNIQUAC and Wilson models. The parameters were also depended on system temperature.