Africanastrongylus giganticus n. sp. is described based on large ostertagiine nematodes occurring in the abomasum of African buffalo, Syncerus caffer, from Uganda; this represents the second species recognized in the genus. Specimens of A. giganticus are characterized by large size (15–19 mm in total length), a strongly tapering synlophe in the cervical region, and a great number of ridges at all levels of the body (maximum 72 attained in the third quarter); numbers of ridges exceed that reported among any known genera and species of the Ostertagiinae. We refer A. giganticus to this genus based on a strongly tapering lateral synlophe, relatively large numbers of ridges at all levels of the body, miniscule cervical papillae, poorly demarcated divisions of the ovejector, absence of vulval cuticular inflations, and the presence of slightly protruding lips at the vulva. It is distinguished from its congener, Africanastrongylus buceros, in total length, maximum number of ridges (68–72 vs. 53, respectively), structure and disposition of the synlophe, presence of strongly spiraled ovarian tracks, and eggs that are distributed in 3 or more rows in the uterus. A superficial resemblance to Longistrongylus meyeri, the only other large ostertagiine in the African fauna, is evident; these species, however, are distinct based on the synlophe and other characters. Recognition of a second species of Africanastrongylus represented by nematodes of large size suggests that prior reports of L. meyeri in Syncerus caffer may be attributable to A. giganticus.