Abstract: Acoustic harassment devices (AHDs) have been increasingly implemented in various fisheries that suffer significant losses caused by odontocete depredation. However, the efficacy of AHDs to deter odontocetes from fishing gear remains poorly investigated. To determine the effectiveness of AHDs in deterring depredation, we experimentally tested a high amplitude device (195 dB re 1 Pa 6.5 kHz 1 m from the source) from a Patagonian toothfish Dissostichus elegenoides longliner operating off the Crozet Islands, while it was subjected to heavy depredation by killer whales Orcinus orca. This species usually depredates longlines within a 10- to 300-m range from the vessel, as they only have access to fishing gear during hauling. We expected this distance to increase in response to the acoustic disturbance created by the AHD. The distances of 29 killer whales from the vessel (n = 1812 records) were collected during phases of AHD activation and phases during which the AHD was turned off. Two multiexposed killer whale social units fled over 700 m away from the vessel when first exposed to the AHD. However, they remained within a 10- to 300-m range and depredated longlines again past the third and seventh exposures, respectively, showing an insignificant behavioural response to further activations of the AHD. When tested through generalized linear mixed models, the effect of AHD activation was only significant when killer whales were first exposed to the device. However, the effect disappeared after successive exposures suggesting that killer whales became habituated to the AHD and may sustain potentially harmful hearing disturbance to access the resource made available by longliners. In addition to raising significant conservation concerns, this rapid return of initial depredation behaviour strongly suggests that AHDs are ineffective at deterring depredating killer whales, and that fisheries should favour the use of other mitigation techniques when facing repeated depredation by this species.