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Despite its ubiquity during the binding and sensing of fluoride, the role of bifluoride (HF2-) and its binding properties are almost always overlooked. Here, we give one of the first examinations of bifluoride recognition in which we use computer-aided design to modify the cavity shape of triazolophanes to better match with HF2-. Computational investigation indicates that HF2- and Cl- should have similar binding affinities to the parent triazolophane in the gas phase. Evaluation of the binding geometries revealed a preference for binding of the linear HF2- along the north–south axis with a smaller Boltzmann weighted population aligned east-west and all states being accessed rapidly through in-plane precessional rotations of the anion. While the ¹H NMR spectroscopy studies are consistent with the calculated structural aspects, binding affinities in solution were determined to be significantly smaller for the bifluoride than the chloride. Computed geometries suggested that a 20° tilting of the bifluoride (stemming from the cavity size) could account for the 25-fold difference between the two binding affinities, HF2- < Cl-. Structural variations to the triazolophane's geometry and electronic modifications to the network of hydrogen bond donors were subsequently screened in a stepwise manner using density functional theory calculations to yield a final design that eliminates the tilting. Correspondingly, the bifluoride's binding affinity (K ∼ 106 M-1) increased and was also found to remain equal to chloride in the gas and solution phases. The new oblate cavity appeared to hold the HF2- in a single east–west arrangement. Our findings demonstrate the promising ability of computer-aided design to fine-tune the structural and electronic match in anion receptors as a means to control the arrangement and binding strength of a desired guest. [ABSTRACT FROM AUTHOR]