The course of the Ohio River for approximately 50 km from New Martinsville to Waverly, West Virginia is controlled by an underlying, subvertical strike-slip fault, the existence of which is evidenced by structure contour maps derived from well data integrated between the Ohio and West Virginia sides of the River based on work by G. Konzen in a University of Dayton undergraduate thesis (available by request). In particular, a north-trending fault-propagation fold, the Burning Springs Arch terminates abruptly at the Ohio River and its northern terminus is inferred to be offset approximately 5 km to the NE where its correlate on the Ohio side of the fault is known as the Cow Creek anticline. Thus, a right-lateral fault is implied with a trend of approximately 060o and a trend of approximately 045o farther to the northeast between Newport, Ohio and Paden City, West Virginia. This fault trend approximately traces the NW margin of the Neoproterozoic Rome Trough and likely reflects a complex and protracted history. However, it is likely that this zone of weakness localized the capture and reversal of the originally north-flowing paleo-Pittsburgh River system by the lower Ohio River drainage system, thus forming the modern Ohio system during the Pleistocene drainage reorganization. Consequently, this suggests the probability that the fault extends to the surface and raises the possibility that it could be active in the contemporaneous stress regime. This area hosts a number of Class II salt water injection wells and several hydraulic fracturing wells in adjacent areas of both Ohio and West Virginia, and a flurry of minor earthquakes up to M 3.0 have been reported in close proximity to the injection wells since 2011. Consequently, a slip-tendency analysis has been undertaken to evaluate the possibility that the Ohio River fault could be active in the contemporaneous stress field. “A-quality†stress determinations from the World Stress Map (Heidbach et al., 2016) within 75 km of the area of interest indicate a vertical maximum principle stress (strike-slip regime) with the maximum horizontal stress oriented between 060o and 090o, apparently rotating toward 090o in the vicinity of the Ohio River. Thus, the fault is likely in the dilational regime ranging to nearly optimally oriented in the contemporary stress field.