These three macrocycles of the same size but varying preorganization and flexibility show that the macrocycle featuring an intermediate flexibility provides the best binding affinity for a range of anions of different size and shape. While several studies reported that more rigidity of preorganized macrocyclic structure provides better affinities, our study illustrates that some flexibility in the macrocycle can be beneficial, in particular for the binding of anions with more complex geometries. This insight will help to guide the design of future generations of macrocyclic receptors for anions or other guests.