Close proximity between humans and large predators results in high levels of conflict. We investigated the extent of, and factors leading to, this conflict through focal group and individual interviews in all villages around Pendjari Biosphere Reserve, northern Benin. Livestock losses from 2000 to 2007 (n = 752) were reported to be mainly caused by spotted hyaena Crocuta crocuta (53.6%), baboon Papio anubis (24.8%), and lion Panthera leo (18.0%). These predators mainly predated sheep and goats (52.1%) and pigs (42.3%), with lions being the main predators of cattle (78.9%). Lion and hyaena diets were more diverse than that of baboons, which killed only small stock. The level of conflict increased during 2000-2007. Predation rate differs between predator species and is significantly influenced by month, rainfall of the month before the predation event, and length of the dry period in a year. The geographical position of the village, the distance of the village to the Park and the number of herbivores legally killed every hunting season also influenced predation intensity. Our findings suggest that improvement of husbandry techniques and education will reduce conflicts and contribute to improved conservation of these threatened predators.