A series of Mb 3.8–5.5 induced seismic events in the midcontinent region, United States, resulted from injection of fluid either into a basal sedimentary reservoir with no underlying confining unit or directly into the underlying crystalline basement complex. The earthquakes probably occurred along faults that were likely critically stressed within the crystalline basement. These faults were located at a considerable distance (up to 10 km) from the injection wells and head increases at the hypocenters were likely relatively small (∼70–150 m). We present a suite of simulations that use a simple hydrogeologic-geomechanical model to assess what hydrogeologic conditions promote or deter induced seismic events within the crystalline basement across the midcontinent. The presence of a confining unit beneath the injection reservoir horizon had the single largest effect in preventing induced seismicity within the underlying crystalline basement. For a crystalline basement having a permeability of 2 × 10−17 m2 and specific storage coefficient of 10−7/m, injection at a rate of 5455 m3/d into the basal aquifer with no underlying basal seal over 10 years resulted in probable brittle failure to depths of about 0.6 km below the injection reservoir. Including a permeable (kz = 10−13 m2) Precambrian normal fault, located 20 m from the injection well, increased the depth of the failure region below the reservoir to 3 km. For a large permeability contrast between a Precambrian thrust fault (10−12 m2) and the surrounding crystalline basement (10−18 m2), the failure region can extend laterally 10 km away from the injection well.