AbstractGas hydrate-bearing sediments (GHBS) are vastly distributed worldwide. Although dissociation of GHBS by depressurization is considered a viable method to produce gas to meet increasing energy demand, it can alter the hydromechanical properties of GHBS by imposing additional stresses on it, which can induce instabilities in the wellbore casing. Despite many short-term gas production trials, the long-term stability and mechanisms of casing–sediment interaction remain unclear. This paper presents a novel centrifuge test using the newly developed energy harvesting chamber to investigate the effects of dissociation on vertical casing–sediment interaction and GHBS response in-flight. Test results reveal that temperature–pressure profiles evolve continuously as hydrate is dissociated, causing extension of dissociation front and inducing changes in effective stress. Dissociation within a perforated interval leads to stress transfer within the formation, resulting in vertical arching. As hydrate dissociation continues, downward movements of soil mobilize negative skin friction. The progressive hydrate dissociation could induce large axial compressive and tensile loads within and above the perforated interval, respectively. The induced axial loads evolve, and the location of neutral planes changes with the progression of hydrate dissociation. During depressurization, the compressive load in the casing exceeds the yield strength of the modeled prototype casing. Although the induced tensile loads are smaller than the yielding strength of the casing, the cement above the perforated interval might crack in tension and jeopardize the well’s integrity. Hence, both induced compressive and tensile axial loads during long-term hydrate dissociation should be carefully considered for safe gas production in GHBS.