The U.S. Atlantic pelagic longline fishery uses a shallow-set gear configuration to primarily target swordfish (Xiphias gladius) and yellowfin tuna (Thunnus albacares) at depths of around 75-100 m. However, the fishery has been the subject of several bycatch reduction regulations due to incidental catch and mortality of sea turtles, seabirds, marine mammals, and istiophorid billfishes. An alternative deep-set technique, used by the U.S. pelagic longline fishery based in Hawaii and several non-U.S. fleets, differs from the shallow-set pelagic longline gear by deploying a greater length of mainline per unit distance using a mechanical line shooter, resulting in a deeper catenary curve and gear that fishes at greater depth in the water column at approximately 200-300 m. Along with the additional length of mainline, deep-set gear typically includes additional hooks per basket (deep-set: 25-30 hooks, shallow-set: 5-10 hooks). In an analysis of 53 deep-sets and 40 shallow-sets, target catch and bycatch per unit effort (CPUE) were compared between shallow and deep-set gear configurations in the U.S. South Atlantic Bight NOAA statistical area. The CPUE of regulated bycatch fishes, including Istiophorid billfishes and some sharks, was lower for deep-set gear while target species CPUE was not significantly different between the two gear types. Additionally, sea turtle and marine mammal bycatch was very low for both gears and no seabird bycatch occurred during this study. Evidence suggests that deep-set gear has potential for bycatch reduction for fishes of concern including istiophorid billfishes and sharks without reducing target catch in the U.S. Atlantic pelagic longline fishery.