The D/H isotope effect for the CH-pi interaction was studied experimentally and computationally. First, a series of molecular balances that are very sensitive to changes in the strength of the CH-pi interactions in solution were designed. Balances with deuterated and non-deuterated alkyl groups were synthesized, and their intramolecular CH-pi interactions were compared. The geometries of their intramolecular CH-pi and CD-pi interactions were characterized in the solid state by X-ray analysis, and the strength of each interaction was characterized in solution by the folded/unfolded ratio as measured by H-1 NMR spectra. Second, the relative strengths of the CH-pi and CD-pi interactions were also assessed computationally using dispersion-corrected DFT (PDE-D2/6-31+G*). No significant differencee was observed in either the experimental or theoretical studies, indicating that the D/H isotope effect for the CH-pi interaction is either very small or nonexistent.