The step by step thermal dehydration process of the zeolite epistilbite from Osilo (Sardinia, Italy), (Ba0.01Sr0.03K0.08Na1.04Ca2.29)[Al5.80 Si18.20O48]-15.8H2O, has been studied in situ by synchrotron radiation powder diffraction. The time-resolved experiment was performed using a translating imaging plate system. Rietveld refinements, based on the average C2/m epistilbite structure, were carried out on 26 consecutive powder patterns in the temperature range from 323 K to 791 K, the upper stability limit of epistilbite in our experiment. Three dehydration steps occur at about 370 K, 470 K and 573 K. The first step is mainly related to the loss of the H2O molecules in the W3 site not directly coordinated to extraframework cations (‘only hydrogen bonded’ water). In the intermediate region between step (a) and (b) epistilbite retains only about 14 water molecules, corresponding to those coordinated to Ca (and Na) ions. Gradual W3, W2, and W1 water losses in step (b) reduce the residual water to about 9 H2O molecules, which is retained up to step (c). This is the minimum water content to maintain the six-coordination of Ca2+ ions. Further water expulsion leads to a first-order phase transition to a collapsed structure (epistilbite B), which has been refined in the C2/m space group. The deformation pattern of the T-O-T angles and the re-arrangement of the extraframework Ca (and Na) cations in epistilbite B suggest a remarkable control exerted by the Si, Al ordering on the thermal stability of epistilbite, whose structural breakdown occurs at very low temperature compared to the related mordenite and ferrierite structures.