The widespread distribution, favorable reservoir characteristics, and depth make the Lower Devonian Oriskany Sandstone a viable sequestration target in the Appalachian Basin. The Oriskany Sandstone is thickest in the structurally complex Ridge and Valley Province, thins toward the northern and western basin margins, and is even absent in other parts of the basin (i.e., the no-sand area of northwestern Pennsylvania). We evaluated four regions using petrographic data, core analyses, and geophysical log analyses. Throughout the entire study area, average porosities range from 1.35 to 14%. The most notable porosity types are primary intergranular, secondary dissolution, and fracture porosity. Intergranular primary porosity dominates at stratigraphic pinch-out zones near the Oriskany no-sand area and at the western limit of the Oriskany Sandstone. Secondary porosity occurs from dissolution of carbonate constituents primarily in the combination-traps natural gas play extending through western Pennsylvania, western West Virginia, and eastern Ohio. Fracture porosity dominates in the central Appalachian Plateau Province and Valley and Ridge Province. Based on average porosity, the most likely regions for successful sequestration in the Oriskany interval are (1) updip from Oriskany Sandstone pinch-outs in eastern Ohio, and (2) western Pennsylvania, western West Virginia, and eastern Ohio where production occurs from a combination of stratigraphic and structural traps. Permeability data, where available, were used to further evaluate the potential of these regions. Permeability ranges from 0.2 to 42.7 md. Stratigraphic pinch-outs at the northern and western limits of the basin have the highest permeabilities. We recommend detailed site assessments when evaluating the sequestration potential of a given injection site based on the variability observed in the Oriskany structure, lithology, and reservoir characteristics.