Trifluoromethylation of higher fullerene mixtures with CF3I was performed in ampoules at 400 to 420 and 550 to 560 °C. HPLC separation followed by crystal growth and X-ray diffraction studies allowed the structure elucidation of nine CF3 derivatives of D2-C84 (isomer 22). Molecular structures of two isomers of C84(22)(CF3)12, two isomers of C84(22)(CF3)14, four isomers of C84(22)(CF3)16, and one isomer of C84(22)(CF3)20 were discussed in terms of their addition patterns and relative formation energies. DFT calculations were also used to predict the most stable molecular structures of lower CF3 derivatives, C84(22)(CF3)2–10. It was found that the addition of CF3 groups to C84(22) is governed by two rules: additions can only occur at para positions of C6(CF3)2 hexagons and no additions can occur at triple-hexagon-junction positions on the fullerene cage.