Cyclodextrins are used in many drug formulations since their cavities provide microenvironments where drug molecules can enter and form inclusion complexes for controlled drug delivery. Supercritical carbon dioxide (scCO 2 ) is an alternative to organic solvents and a very attractive medium for the preparation of these inclusion complexes. The potential ability of triacetyl-β-cyclodextrin (TA-β-CD) to form inclusion complexes in addition to its high miscibility in liquid and scCO 2 could offer a chance for an economical and environmental friendly chemical processing. In this work, high-pressure NMR studies were performed in order to obtain information on the molecular structure and dynamics of TA-β-CD in scCO 2 at 313.15 K and 20 MPa and its ability to form inclusion complexes under these conditions was studied. The influence of scCO 2 on a number of NMR spectral parameters, such as chemical shifts, spin-spin coupling constants, nuclear Overhauser effect (NOE) and spin-lattice relaxation (T 1 ) has been studied. We unequivocally show for the first time structural changes of TA-β-CD in scCO 2 , like acetyl chain orientation and overall shape distortions that can affect its inclusion capability in this medium. The possibility of cavity self-closure is discussed and the results of two inclusion studies that support cavity self-closure, with the angiotensin-converting enzyme inhibitor, captopril, and the nonsteroid anti-inflammatory drug, flufenamic acid, are presented.