CO2 injection in extensive saline aquifers that present no faults is unlikely to damage the caprock sealing capacity. In contrast, CO2 injection in closed reservoirs will induce a large pressure buildup that may reactivate the low-permeable faults that bound the reservoir. However, the vast majority of CO2 storage formations will be extensive saline aquifers bounded by a limited number of low-permeable faults. Such storage formations have received little attention and are the focus of this study. We model an extensive aquifer bounded by a heterogeneous low-permeable fault on one side and having open boundaries on the other sides. Simulation results show that the storage formation pressurizes between the injection well and the low-permeable fault, causing total stress changes and effective stress reduction around the fault. These changes lead to yielding of the fault core that is next to the lower half of the storage formation when injecting in the hanging wall. The yield of the fault core would induce a sequence of microseismic events with accumulated seismic moment equivalent to an earthquake of magnitude 1.7, which would not be felt on the ground surface and would not enhance permeability of the ductile clay-rich fault. © 2017 The Authors. V.V. acknowledges support from the ‘EPFL Fellows’ fellowship programme co-funded by Marie Curie, FP7 Grant agreement no. 291771. R.M. activities are sponsored by SCCER-SoE (Switzerland) grant KTI.2013.288 and Swiss Federal Office of Energy (SFOE) project CAPROCK #810008154. Peer reviewed