Injection or withdrawal of fluid at depth may trigger felt seismicity. Such human-induced seismicity is a key environmental concern related to the exploitation of natural underground resources. Thus, understanding how to avoid triggering felt earthquakes plays a crucial role in the success of underground anthropogenic activities, such as CO2 geological storage. In this work, we conduct 3D simulations of injection-triggered fault reactivation, in order to investigate the effects of well geometry on seismic rupture and CO2 leakage. We analyze two different cases of injection, through (1) a vertical and (2) a horizontal well. Simulation results for the vertical well show the fault pressurizing faster and more locally than for the horizontal well, resulting in a smaller seismic event. For the horizontal well, the pressure is distributed over a wider area along the fault, which requires a longer time to reactivate, but results in a larger event. Fault reactivation also produces changes in damage-zone and fault-core permeability, allowing the CO2 to leak from the injection zone through overlying caprock, toward shallower depths. Although the calculated fault permeability enhancement is similar for the two cases, results show a slightly higher leakage rate for the vertical well in the region close to the well itself, while the leakage resulting from injection through the horizontal well is more widely distributed.Published 2015. This article is a U.S. Government work and is in the public domain in the USA.