The complexation of alkaline-earth metal cations with tertiary-amide lower-rim fluorescent calix[4]arene derivative comprising two phenanthridine moieties was studied by means of spectrophotometric, fluorimetric, and microcalorimetric direct and competitive titrations. In order to investigate the solvent effect on cation-binding processes, the complexation reactions were studied in acetonitrile, methanol, and ethanol, whereby the complex stability constants (and derived standard reaction Gibbs energies) as well as standard reaction enthalpies and entropies of complexation reactions were determined. The investigated calixarene exhibited high affinity towards alkaline-earth metal cations in acetonitrile, with low selectivity and peak affinity corresponding to Ca2+, whereas the complex stabilities were significantly lower in ethanol and methanol, in which the affinity for Sr2+ was highest. The differences in cation-binding abilities were a consequence of the differences in solvation of the species present in solution as well in compatibility of the cation and binding-site sizes. The extensive solvent effect could be, at least partially, rationalized by much more favourable cation solvation in methanol and ethanol, as compared to acetonitrile. The binding reactions were enthalpically controlled in acetonitrile, as opposed to methanol and ethanol in which the reactions were endothermic and entropically driven. The investigated ligand was proven to be very effective and rather sensitive fluorescent receptor for Ca2+ and Sr2+ in acetonitrile.