Consumption by multiple conspecific or interspecific predators on shared prey is not always predicted when data from isolated predators are combined. Predator interactions can result in non-independent predator effects on prey, and may be influenced by prey size selection and bottom type. We examined stone crab Menippe mercenaria and blue crab Callinectes sapidus predation of hard clams Mercenaria mercenaria. Interactions between these predators may become common in mid-Atlantic estuaries as stone crab abundance increases with a poleward range shift driven by climate change. Crabs in isolation, in conspecific pairs and in the interspecific pair were offered clams in 5 size classes simultaneously (10–60 mm shell length [SL]) or 1 size class (10–20 mm SL). Trials were on sand and hard bottom. On sand, all predator pairs had independent effects on prey, regardless of the presence or absence of multiple prey sizes. On hard bottom, when multiple prey sizes were present, blue crab conspecific and the interspecific pairs consumed less than predicted from isolated crabs. Strong selection of small clams by blue crabs led to conspecific interactions that reduced foraging compared to isolated crabs. Because stone crabs consumed all clam sizes, behaviours other than prey size selection caused the non-independent effect on prey by the interspecific pair. When multiple prey sizes were absent on hard bottom, most predator pairs had independent effects on prey. Thus, an expected poleward range shift of stone crabs may not increase interactions with blue crabs when foraging on sand. However, on hard bottom, increased predator interactions could reduce overall predation risk for prey, especially when consuming multiple prey sizes. In a climate-changed mid-Atlantic estuary, stone crabs will consume a wide range of clam sizes, and the size refuge large clams usually have from blue crab predation will be lost.