This species is widespread on relatively deep non-calcareous soils of the Coastal Plain and Piedmont east of the Mississippi Rv. It was originally described from "West Kentucky. to Louisiana" by Rafinesque (1830, 1832), but no potential type collection is known; he had earlier listed it without detail as Cactus mesacantha in 1821 (Western Minerva p. 41). The closest verified records to Ky. are from the Coastal Plain of sw. Tenn. Majure et al. (2017) doubted Rafinesque's report from Ky., but his citations are confusing. Moreover, potential habitat may have existed on the Coastal Plain in Ky. within the extensive native grassland that formerly occurred here. O. mesacantha is a tetraploid with usually all-yellow flowers like humifusa, but it differs as follows (Majure 2017): cladodes with (generally) or without (especially in Ala. and Ga.) spines (versus spineless), mostly obovate, rotund or elliptical (versus rotund or elliptical), the areoles generally 3-4 per along widest diagonal row (versus 4-5), the glochids mostly exerted (versus included). Its diploid relative, O. lata Small, is more southern, but close enough to be considered a subspecies by Majure et al. (2017). Without flowers, mesacantha is still distinguishable from cespitosa as follows; cladodes (pads) are dark to paler yellowish green (versus glaucous when developing); spines are retrorsely barbed when young (versus not so), brown-white mottled during development (versus reddish-brown at base); glochids are straminous to light brown (versus dark red to brown).