CSD- and PDB-wide surveys of CF3-containing compounds have identified very divergent rates of isostructrality between CH3/CF3 analogues and a variety of behaviors for the CF3 groups ranging from nucleophilic to electrophilic. We present 13 crystal structures containing the 4-trifluorotoluenesulfonamide (F3TsN) moiety and then analyze these structures and 10 pairs of CF3/CH3 toluenesulfonamide analogues using PIXEL-calculated lattice energies, Hirshfeld surfaces, ratios of frequencies, and electrostatic potential energy maps. The F3TsN group is directly and representatively interesting from a pharmaceutical context, given its strong additional intermolecular forces (H bonding and π stacking). Unsurprisingly, many C–F···F angles correspond to type I halogen–halogen interactions, with several presenting at distances shorter than the sum of the van der Waals radii. Only 1 of 10 pairs in our study are isostructural, likely resulting from numerous but individually weak F···H and F···C intermolecular interactions. A ratio of frequencies analysis shows that C­[unsat]–F contacts occur much more frequently in F3Ts structures than in the general population of fluorinated structures. We suggest that a detailed analysis of increasing pools of structural data for specific moieties can complement database-wide surveys and lead to more definitive conclusions and eventually design principles.