Accurate bond dissociation energies for large molecules are difficult to obtain by either experimental or computational methods. The former methods are hampered by a range of physical and practical limitations in gas-phase measurement techniques, while the latter require incorporation of multiple approximations whose impact on accuracy may not always be clear. When internal benchmarks are not available, one hopes that experiment and theory can mutually support each other. A recent report found, however, a large discrepancy between gas-phase bond dissociation energies, measured mass spectrometrically, and the corresponding quantities computed using density functional theory (DFT)-D3 and DLPNO-CCSD(T) methods. With the widespread application of these computational methods to large molecular systems, the discrepancy needs to be resolved. We report a series of experimental studies that validate the mass spectrometric methods from small to large ions and find that bond dissociation energies extracted from threshold collision-induced dissociation experiments on large ions do indeed behave correctly. The implications for the computational studies are discussed.