This study investigates the hydro-mechanical aspects of carbon dioxide (CO2) injection into a depleted oil reservoir through the use of coupled multiphase fluid flow and geomechanical modeling. Both single-phase and multiphase fluid flow analyses coupled with geomechanics were carried out at the West Pearl Queen depleted oil reservoir site, and modeling results were compared with available measured data. The site geology and the material properties determined on the basis of available geophysical data were used in the analyses. Modeling results from the coupled multiphase fluid flow and geomechanical analyses show that computed fluid pressures match well with available measured data. The hydro-mechanical properties of the reservoir have a significant influence on computed fluid pressures and surface deformations. Hence, an accurate geologic characterization of the sequestration site and determination of engineering properties are important issues for the reliability of model predictions. The computed fluid pressure response is also significantly influenced by the relative permeability curves used in multiphase fluid flow models. While the multiphase fluid flow models provide more accurate fluid pressure response, single-phase fluid flow models can be used to obtain approximate solutions. The ground surface deformations obtained from single-phase fluid flow models coupled with geomechanics are slightly lower than those predicted by multiphase fluid flow models coupled with geomechanics. However, the advantage of a single-phase model is the simplicity. Limited field monitoring of subsurface fluid pressure and ground surface deformations during fluid injection can be used in calibrating coupled fluid flow and geomechanical models. The calibrated models can be used for investigating the performance of large-scale CO2 storage in depleted oil reservoirs.