Abstract: Marine mammal depredation on fisheries (animals removing fish caught on fishing gear) is a worldwide issue involving socio-economic and ecological consequences. Longline fisheries are the most impacted by odontocete (toothed whales) depredation. While technological means have provided limited efficacy in reducing depredation, this study examined the fishing practices influencing both the proportion of depredated longline sets and the amount of fish removed by whales. We used an 8-year dataset from the Patagonian toothfish (Dissostichus eleginoides) longline fisheries operating in Crozet and Kerguelen Economic Exclusive Zones (EEZs) (South Indian Ocean) and GLMMs to investigate sperm whale (Physeter macrocephalus) depredation. Sperm whale depredation occurred on 61% of 5260 sets in Crozet and 41% of 16,902 sets in Kerguelen, and resulted in minimum estimated toothfish losses of 702 tons and 2649 tons, respectively, in the two areas. The probability of depredation decreased in winter months, increased with depth fished and decreased when vessels travelled over distances of >60?km from fishing grounds with encountering depredation. These findings suggest the natural spatio-temporal distribution of sperm whales and their ability to follow vessels over limited ranges influence the number of captured fish removals. The amount of depredated toothfish decreased with the speed at which longline sets were hauled and increased with the soaking time of sets suggesting that whales may depredate sets during both hauling and soaking operations. Together, these observations indicate that rates of depredation may be influenced by the conditions of fishing operations and could therefore be employed to implement strategies of avoidance in all fisheries facing similar depredation impacts.