Leakage of CO2 and associated gases into overlying aquifers as a result of geologic carbon capture and sequestration may have adverse impacts on aquifer drinking-water quality. Gas or aqueous-phase leakage may occur due to transport via faults and fractures, through faulty well bores, or through leaky confining materials. Contaminants of concern include aqueous salts and dissolved solids, gaseous or aqueous-phase organic contaminants, and acidic gas or aqueous-phase fluids that can liberate metals from aquifer minerals. Here we present a quantitative risk assessment framework to predict potential human health risk from CO2 leakage into drinking water aquifers. This framework incorporates the potential release of CO2 into the drinking water aquifer; mobilization of metals due to a decrease in pH; transport of these metals down gradient to municipal receptors; distributions of contaminated groundwater to multiple households; and exposure and health risk to individuals using this water for household purposes. Additionally, this framework is stochastic, incorporates detailed variations in geological and geostatistical parameters and discriminates between uncertain and variable parameters using a two-stage, or nested, Monte Carlo approach. This approach is demonstrated using example simulations with hypothetical, yet realistic, aquifer characteristics and leakage scenarios. These example simulations show a greater risk for arsenic than for lead for both cancer and non-cancer endpoints, an unexpected finding given greater toxicity of lead at lower doses than arsenic. It was also found that higher background groundwater gradients also yield higher risk. The overall risk and the associated uncertainty are sensitive to the extent of aquifer stratification and the degree of local-scale dispersion. These results all highlight the importance of hydrologic modeling in risk assessment. A linear relationship between carcinogenic and noncarcinogenic risk was found for arsenic and suggests action levels for carcinogenic risk will be exceeded in exposure situations before noncarcinogenic action levels, a reflection of the ratio of cancer and non-cancer toxicity values. Finally, implications for ranking aquifer vulnerability due to geologic configuration, aquifer mineralogy, and leakage scenarios are discussed.