Problem Animal Control Registers, where farmers report livestock losses due to predators as a prerequisite for financial compensation, allow quantifying the human–predator conflict. We analyzed such registers from the Kweneng District of Botswana to assess the impact of native predators on livestock over 3 years. Leopards (Panthera pardus), lions (Panthera leo), wild dogs (Lycaon pictus), brown hyenas (Hyaena brunnea), and cheetahs (Acinonyx jubatus) altogether claimed 2,272 head of livestock. During 2002, the year with the highest impact, the number of animals reported depredated (954) represented 0.34% of the livestock in the district. Leopards and lions caused 64% of the losses. Leopard livestock predation mainly affected calves and was consistent over the district and over time. In contrast, lion predation concentrated on adult cattle, was characterized by local hot spots close to reserve borders, decreased with increasing distance to a reserve, and increased during 2002, an unusually dry year. Interviews with 60 farmers and herders within 30 km of Khutse and Central Kalahari Game Reserves revealed an annual loss of 2.2% of their livestock to predators. Here, small farms (max. 100 domestic animals) suffered relatively higher losses than large, commercial farms, not only due to predation (small farms: 11.7%; large farms: 1.0%) but also from other causes (small: 12.6%; large: 2.8%), even though herders on large farms guarded 5 times more livestock per person than those on small farms. To reduce livestock predation in most of the district where lions are absent, we recommend maternity corrals for pregnant females and calves to better protect vulnerable calves during day and night. In areas close to a reserve where lions roam, herders' incentives to keep all livestock protected in a corral at night have to be enhanced because, according to the registers, only 3 predation cases were reported to have happened inside a corral.