The Flory interaction parameters chi for blends of random copolymers consisting of binary combinations of methyl methacrylate (MMA), n-butyl methacrylate (nBMA), and isobutyl methacrylate (iBMA) monomers were calculated using the Flory equation-of-state theory with modified combining rules extended to random copolymer systems. In order to determine the intersegmental or intermolecular parameters necessary for the calculation of chi for the blends, osmotic pressures, heats of mixing at infinite dilution, and excess volumes of mixing for solutions of the methacrylate random copolymers in cyclohexanone were measured, and the equation-of-state theory was applied to these solutions. Using the intersegmental parameters thereby determined, the theory gives U-shaped curves for the temperature dependence of chi for the blends. Namely, the theory shows that miscibility of these polymer blends is of the upper critical solution temperature type, which is consistent with the miscibility results obtained experimentally in our previous work. The interaction parameters chi calculated for PiBMA/PnBMA were much smaller than those for PMMA/PiBMA and PMMA/PnBMA. This result is also consistent with the experimental results of miscibility. The calculated chi parameters were compared with those evaluated using two other methods, i.e., from the dependence of miscibility on the copolymer composition of the random copolymer blends and from the osmotic pressures for the random copolymer solutions. It was found that the chi values obtained using all three methods were nearly the same.