The rotational isomerism of calix[4]arene, 25,27-dihydroxy-26,28-dimethoxycalix[4]arene, and 25,26,27,28-tetramethoxycalix[4]arene in different environments has been examined using sophisticated ab initio and DFT calculations. Free energies in the gas phase, in chloroform, and in toluene have been calculated not only for the minimum energy conformations cone and paco, which differ in the orientation of one phenol/anisole ring with respect to the other three, but also for the transition state that connects these two minima. Results provide a complete understanding of the changes induced by the partial or total OH -> OCH3 replacement in the calix[4]arene scaffold.