Abstract: Crown ethers are a group of important host compounds that receive vast applications in areas such as supramolecular recognition and metal separation. The substituents on crown ethers are expected to have great impacts on the complexation ability to metal ions by crown ethers. In this work, the complexation of three structurally related 18-crown-6 ligands with Nd³⁺ in acetonitrile was experimentally studied through UV-Vis spectroscopy and microcalorimetry. The impact of phenyl group attached to the crown ethers on the complexation was evaluated. The results indicate that all the three crown ethers form 1∶1 complex with Nd³⁺. The complexation reaction is driven by positive entropies but opposed by endothermic enthalpies. The phenyl group lowers the complexation ability of crown ethers to Nd³⁺. Moreover, the complexation behavior of Nd³⁺ and Am³⁺ with the three crown ethers was compared through DFT calculations. Nd³⁺ is found to exhibit slightly stronger interactions with the same crown ether than Am³⁺, which may be attributed to the slight difference in ionic size between Nd³⁺ and Am³⁺ that enables more favorable size match of Nd³⁺ with the crown ethers.