The first theoretical study on the effects of ligands on the mechanism, reactivities, and regioselectivities of Rh(I)-catalyzed (5 + 2) cycloadditions of vinylcyclopropanes (VCPs) and alkynes has been performed using density functional theory (DFT) calculations. Highly efficient and selective intermolecular (5 + 2) cycloadditions of VCPs and alkynes have been achieved recently using two novel rhodium catalysts, [Rh(dnCOT)]+SbF6- and [Rh(COD)]+SbF6-, which provide superior reactivities and regioselectivities relative to that of the previously reported [Rh(CO)(2)Cl](2) catalyst. Computationally, the high reactivities of the dnCOT and COD ligands are attributed to the steric repulsions that destabilize the Rh-product complex, the catalyst resting state in the catalytic cycle. The regioselectivities of reactions with various alkynes and different Rh catalysts a:re investigated, and a predictive model is provided that describes substrate substrate and ligand-substrate steric repulsions, electronic effects, and noncovalent pi/pi and C-H/pi interactions. In the reactions with dnCOT or COD ligands, the first new C-C bond is formed proximal to the bulky substituent on the alkyne to avoid ligand-substrate steric repulsions. This regioselectivity is reversed either by employing the smaller [Rh(CO)(2)Cl](2) catalyst to diminish the ligand-substrate repulsions or by using aryl alkynes, for which the ligand-substrate interactions become stabilizing due to pi/pi and C-H/pi dispersion interactions. Electron-withdrawing groups on the alkyne prefer to be proximal to the first new C-C bond to maximize metal substrate back-bonding interactions. These steric, electronic, and dispersion effects can all be utilized in designing new ligands to provide regiochemical control over product formation with high selectivities. The computational studies reveal the potential of employing the dnCOT family of ligands to achieve unique regiochemical control due to the steric influences and dispersion interactions associated with the rigid aryl substituents on the ligand.