Prenanthes crepidinea is generally recognized by its tall and robust habit, large deltate or ovate proximal leaves, coarsely dentate margins with relatively large, remote teeth, heads borne in open, paniculiform arrays, dark green or blackish and moderately to densely setose phyllaries, and white or yellow corollas. In some areas P. crepidinea and P. serpentaria overlap in leaf morphology and corolla color, perhaps indicative of past hybridization, and can be difficult to distinguish. Prenanthes serpentaria is generally smaller in stature, has more elongate, pinnately lobed leaves with rounded sinuses, more sparsely setose phyllaries, and yellow or greenish yellow corollas. Prenanthes crepidinea appears to favor moist, bottomland sites, in contrast to the drier and acidic upland habitats preferred by P. serpentaria. Prenanthes crepidinea appears to hybridize with P. aspera in southeastern Missouri (J. A. Steyermark 1963).