Large, mesopelagic teleosts have a potentially keystone position in the ecology of the pelagic water column, yet remain relatively unstudied when compared to large, commercially important fishes of the epipelagic zone. In this study, the ecological roles of four large, vertically migrating teleosts, oilfish, Ruvettus pretiosus, escolar, Lepidocybium flavobrunneum, snake mackerel, Gempylus serpens, longnose lancetfish, Alepisaurus ferox, and shortnose lancetfish, Alepisaurus brevirostris, were examined. The stomachs of 61 oilfish, 35 escolar, 33 snake mackerel, and 34 lancetfish were collected from nighttime, pelagic, longline fishing operations in the epipelagic zone of the western North Atlantic Ocean and Gulf of Mexico from 2007 to 2010. Stomach content analysis was used to determine predator-prey interactions. Stable carbon and nitrogen isotope analyses were performed on white dorsal muscle tissue of 38 oilfish, 23 escolar, 28 snake mackerel, and 19 lancetfish also sampled for stomach content analysis. Crustaceans were abundant prey of small oilfish, lancetfish, and to a lesser degree, snake mackerel, and they were absent from large escolar diets. Lancetfish and snake mackerel showed diverse diets that included crustaceans, polychaetes, gymnosomes, salps, cephalopods, and fishes. Large escolar stomachs contained only squid and fish. Stable isotope analyses placed small oilfish in the lowest trophic position of the group, followed by lancetfish and snake mackerel, and large escolar occupied the highest trophic position of the four species.