In the specific case study used here, we obtain clear evidence that the reaction acceleration is controlled by the crowding effects accompanying the guest encapsulation. We compared four cases, where the amide guest 2 is alone in solution, when it is encapsulated in the cage (2 ⇢ 1), or when it is co-encapsulated together with other co-guests in the cage cavity (2 2 ⇢ 1 and 2 • 3 ⇢ 1), we characterized all of them, and we estimated their hydrolysis acceleration factor. The results show unambiguously that the encapsulation of the amide in the cage cavity tends to stabilize the reactive conformers of the amide guest. This is key in such specific systems, considered the high encapsulation constants obtained for all studied cases (i.e., high probability to find the amide guest within the cage cavity).