The gas phase protonation of SF₅CF₃, a potent new greenhouse gas recently discovered in stratospheric air samples, was studied by the joint application of mass spectrometric and ab initio theoretical methods. The reaction is essentially dissociative leading to the formation of HF, CF₄ and SF₃⁺ as main fragmentation products. Consistent with collisionally activated dissociation (CAD) mass spectrometric results, theoretical calculations identified the loosely bounded ion–molecule complex [HF–SF₄–CF₃], I, as the most stable isomer on the [SF₅CF₃]H⁺ potential energy surface. The proton affinity of SF₅CF₃ estimated from FT-ICR ‘bracketing’ experiments was found to be 152.5 ± 3 kcal mol⁻¹ which agrees with the values obtained from theoretical calculations at B3LYP and CCSD(T) levels of theory, 154.0 ± 3 and 153.4 ± 3 kcal mol⁻¹, respectively. These results suggest that the basicity of SF₅CF₃ is higher than that of atmospheric cations such as H₂O⁺; they need to be considered when evaluating the lifetime of SF₅CF₃ since it can be destroyed by proton transfer reactions.