Whether nonconventional hydrogen bonds, such as the C–H···O interaction, are a consequence or a determinant of conformation is a long-running and unresolved issue. Here we outline a solid-state and quantum mechanical study designed to investigate whether a C–H···O interaction can override the significant trans-planar conformational preferences of α-fluoroamide substituents. A profound change in dihedral angle from trans-planar(OCCF) to cis-planar(OCCF) observed on introducing an acceptor group for a C–H···O hydrogen bond is consistent with this interaction functioning as a determinant of conformation in certain systems. This testifies to the potential influence of the C–H···O hydrogen bond and is consistent with the assignment of this interaction as a contributor to overall conformation in both model and natural systems.