We present difference-dedicated second-order vibrational perturbation theory (VPT2) as an efficient method for the computation of nuclear magnetic resonance (NMR) isotopic shifts, which reflect the geometry dependence of the NMR property in combination with different vibration patterns of two isotopologues. Conventional calculations of isotopic shifts, e.g., by standard VPT2, require scanning the geometry dependence over the whole molecule, which becomes expensive rapidly as the molecule size increases. In DD-VPT2, this scan can be restricted to a small region around the substitution site. At the heart of DD-VPT2 is a set of localized vibration modes common to the two isotopologues and designed such that the difference between the vibration patterns is caught by a small subset of them (usually fewer than 10). We tested the DD-VPT2 method for a series of molecules with increasing size and found that this method provides results with the same quality as VPT2 and in good agreement with the experiment, with computational savings up to 95% and less numerical instabilities. The method is easy to automatize and straightforward to generalize to other molecular properties.