Significance A widespread strategy used by prey animals, seen in insects, mammals, amphibians, crustaceans, fish, and reptiles, is to vary the direction in which they escape when attacked by a predator. This unpredictability is thought to benefit prey by inhibiting predators from predicting the prey’s escape trajectory, but experimental evidence is lacking. Using fish predators repeatedly tested with interactive, robot-controlled prey escaping in the same (predictable) or in random (unpredictable) directions, we find no clear benefit to prey of escaping unpredictably, driven by behavioral counteradaptation by the predators. The benefit of unpredictable escape behavior may depend on whether predators are able to counteract prey escape tactics by flexibly modifying their behavior, or unpredictability may instead be explained biomechanical or sensory constraints.