Nonlocal density functional calculations have been used to compare the stabilities of metalloporphyrin isomers as a function of metal ion size, divalent Ni, Zn, Pd, and Cd ions having been examined. Ordinary porphyrin is found to form the most stable bis-N-deprotonated dianions and metal complexes compared to the other isomeric ligands, a finding of potential relevance to the question of why Nature has chosen porphyrin-based cofactors. The various dianionic ligands may be ranked as follows in increasing order of relative energy : [1.1.1.1] < [2.1.1.0] < [2.0.2.0] < [2.1.0.1] < trans-[3.0.1.0] < cis-[3.0.1.0]. This order differs from that of the stabilities of the free bases. An interesting result reminescent of a recent study of corrole isomers is that the order of stabilities of the isomeric metalloporphyrins is metal-dependent and undergoes reversals with changing size of the coordinated metal ion. Thus, the small Ni(II) ion forms the most stable complex with the [2.0.2.0] porphyrin isomer (with the exception of normal porphyrin) and relatively higher-energy complexes with the [2.1.0.1] Ligand. In contrast, the Cd(II) ion forms relatively stable complexes with the [2.1.0.1] porphyrin isomer and relatively unstable complexes with the [2.0.2.0] ligand. Another interesting result concerns cis-trans isomerism of the [3.0.1.0] skeleton : the trans-[3.0.1.0] ligand forms increasingly more stable complexes relative to the cis stereoisomeric ligand with increasing size of the coordinated metal ion.