A density functional theory (DFT) study was performed to elucidate the mechanism of the Ni-catalyzed [3 + 2 + 2] Cyclization reaction of cyclo-propylideneacetate with two alkynes. A systematic search showed that the nature of the alkynes determines the choice between two reaction pathways and hence the regioselectivity. Strongly electron-deficient acetylenes preferentially afford 2,5-disubstituted products via nickel-acyclopentadienes generated by [2 + 2] cocyclization, whereas normal alkynes afford 3,4 or 3,5-products via an unprecedented pathway involving a [3 + 2] nickelacycle intermediate.