In this paper, we rationalize the thermodynamics behind the guest-induced structural transitions of hybrid material showing that the existence of a double transition depends on the relatiVe guest affinities for the two phases, rather than absolute adsorption enthalpies. Based on a simple model, we interpret recent experimental data on alkane adsorption and predict transition pressures.Porous metal-organic frameworks (MOFs) are a topical class of materials that display an extremely large range of crystal structures and host-guest properties, potentially giving them a major impact in adsorption, separation, and storage of strategic gases (H 2 , CO 2 , CH 4 ,...). A growing number of these materials show exceptional guest-responsive behaviors upon gas adsorption, due to the flexibility of their organic-inorganic frameworks. This includes examples of progressive swelling or contraction (also called breathing), pore deformation, and amorphous-to-crystal and crystalto-crystal structural transitions.1 The MIL-53 materials family, 2 a particularly eye-catching case of the last category, has attracted a lot of attention due to its large flexibility and the occurrence of a double structural transition upon adsorption of some gases (CO 2 , H 2 O, C 2 H 6 ,...) but not others (H 2 , CH 4 ).3 It was also reported very recently 4 that liquid phase adsorption of para-xylene does induce a structural transition, while ortho-and meta-xylene do not. The studies performed so far, both experimentally and by molecular simulation, mainly focused on structural characterization and energetics (by calorimetry, forcefield-based calculations and DFT). However, the current depiction of these guest-induced structural transitions is lacking a general thermodynamic interpretation of all the results obtained so far; Llewellyn et al. indeed highlighted the necessity of understanding "the thermodynamic conditions for the host-guest interactions which allow the breathing to happen". 3 We recently developed a generic thermodynamic framework for the understanding of guest-induced structural transitions in flexible nanoporous materials such as MOFs, 5 by use of the osmotic pseudoensemble. For a material that has two possible framework structures and where gas adsorption follows type I isotherms, 6 we proposed a full taxonomy of possible guest-induced structural transitions. This classification relies only on a few key parameters, such as the free energy difference, ∆F, between the (empty) host structures, their pore volumes, V p (i) , and the adsorption affinities for the guest, K i . This method also allows us to calculate one of these parameters when the pressures of structural transitions are known. The robustness of the method was demonstrated on systems exhibiting such contrasting behaviors as "breathing" and "gate opening". In the case of MIL-53 (Al), in particular, we used the available CO 2 adsorption isotherm to calculate a free energy difference between the empty large pore (lp, Figure 1S) and narrow pore (np, Figure 2S) forms of ∆F ≈ 2....