© 2015. Large-scale pressure increases resulting from carbon dioxide (CO2) injection in the subsurface can potentially impact caprock integrity, induce reactivation of critically stressed faults, and drive CO2 or brine through conductive features into shallow groundwater. Pressure management involving the extraction of native fluids from storage formations can be used to reduce such pressure increases. However, dealing with large volumes of extracted brine can be technically challenging and expensive. Selection of optimal well locations and pumping rates are critical for maximizing CO2 storage and minimizing brine extraction during geologic CO2 sequestration (GCS). Robust and efficient computerized algorithms combining reservoir models and optimization methods are needed to make proper decisions on well placement and pumping rates. This study presents a constrained differential evolution (CDE) algorithm for solving global optimization problems involving pressure management of GCS projects. Application of the CDE optimization methodology was demonstrated for a hypothetical CO2 storage scenario in a deep sandstone reservoir in the Southern San Joaquin Basin in California, USA. Industrial-scale storage of CO2 would generate significant pressure buildup in this formation, which in turn would raise concerns about induced seismicity due to presence of multiple faults surrounding the injection site. Through the CDE optimization algorithm coupled to a vertically-averaged reservoir simulator, we successfully estimated optimal solutions for brine extraction wells in the reservoir that would limit the local pressure along the faults to a prescribed threshold. Multiple realizations of the reservoir permeability field were created to understand the impact of reservoir heterogeneity on optimization results. Our results indicate that the reservoir slope and heterogeneity have significant impact on optimum extraction rates. Reservoir heterogeneity is also a significant factor for extraction well locations, suggesting that in practice decisions about extraction well placement through optimization should be made at later project stages when data from a few years of CO2 injection have allowed iterative updating and refining of the reservoir forward models. Although the study focused on optimization of brine extraction, the CDE optimization methodology presented in this paper has also potential to solve other complex optimization problems related to GCS, such as increasing storage efficiency by enhancing injectivity and capillary and dissolution trapping.