A combined experimental and theoretical investigation revealed mechanistic differences in the ring-opening polymerization (ROP) behavior of macrocyclic carbonates (MCs, 11-membered to 15-membered MCs). The study employs urea and potassium methoxide as the catalytic system for ROP. Besides the polymerization rate correlating with the ring size, where smaller rings have a faster polymerization rate, both the thermodynamic stability of the conformer and the stability of the transition state affect the polymerization rate. An experimental kinetic evaluation revealed a deviation between the polymerization rate of the 11-membered MC and the rest of the MCs. Computational investigation using density functional theory showed that the thermodynamic stability of the 11-membered MC differs from others, with a population distribution more toward the usually less energetically disfavored (E,Z)conformer, while the larger rings showed a preference for the Z,Z-conformation. In the transition state, the (E,Z)-conformer was found to be lower in energy compared to the (Z,Z)-conformation, which leads to a lower Gibbs free energy of activation for nucleophilic attack on the (E,Z)-conformation (Delta G(+/-) = 18.3 kcal center dot mol(-1)) compared to macrocycles with the more stable (Z,Z)-conformation (19.8 kcal center dot mol(-1)). The rate-determining step for the 11-membered MC with (E,Z)-conformation relates to the nucleophilic addition, while the rate-limiting step for the larger 15-membered MC corresponds to the ring-opening step. Linking the thermodynamic conformer stability of cyclic monomers to their inherent polymerization behavior is essential for the future design of selective catalysts for ROP.