Hemis National Park of the Trans-Himalayas is home to a large population of the snow leopard Panthera uncia and increasing numbers of agro-pastoralists. To persist in this harsh terrain, farmers have to either farm livestock or hunt free-ranging, native ungulates. The availability of more livestock and fewer natural prey created a dynamic whereby snow leopards depredated livestock, followed by retaliatory killing of snow leopards. In 1992, to assist farmers and wildlife, the government enacted a cost-compensation scheme. Following a decade with marginally fewer depredation events, in 2002, two additional strategies were implemented: predator-proof holding pens and the Himalayan Homestay Programme. We assessed 22 years (1992–2013) of depredation data, comparing the periods before and after the additional initiatives. Government records showed that during 1992–2013, 1,624 livestock were depredated from 339 sites, with c. USD 15,000 paid as compensation. There were significantly more kills annually before (a mean of 41) than after (3.5) the initiatives, and mass killings (≥ 5 animals killed per attack) were significantly reduced from 5.5 to 0.5 events per year. Goats and sheep (57%) and horses (13%) comprised the majority of losses. The marked reduction in depredation occurred whilst regulations against hunting were being enforced, probably resulting in an increase in the number of wild prey as alternative food. We conclude that together, cost-compensation, tighter hunting regulations, improved holding pens and the Homestay Programme helped support the well-being of the community while aiding conservation efforts.