Human-wildlife conflicts are widespread, particularly with big cats which can kill domestic livestock and create a counteraction between conservation and local livelihoods, especially near protected areas. Minimization of livestock losses caused by big cats and other predators is essential to mitigate conflicts and promote socially acceptable conservation. As big cats usually kill by throat bites, protective collars represent a potentially effective non-lethal intervention to prevent livestock depredation, yet the application and effectiveness estimation of these tools are very limited. In this study, for the first time we measured the effectiveness of studded leather collars in protecting cattle from leopard (Panthera pardus) attacks. We conducted a randomized controlled experiment during 14 months to collar 202 heads and leave uncollared 258 heads grazing in forests and belonging to 27 owners from eight villages near three protected areas in Mazandaran Province, northern Iran. Our results show that none of collared cattle and nine uncollared cattle were lost to leopard depredation, meaning that collars caused a zero relative risk of damage and a perfect 100% damage reduction. Most losses occurred in summer and autumn due to lush vegetation attracting more cattle, long daytime allowing movements deep into leopard habitats, and dense cover favoring leopard hunts from ambush. Losses were recorded in only six owners and four villages, suggesting local rarity and patchy distribution of leopards. We suggest that collars can be successfully applied to cattle freely grazing in habitats of leopards or other felids for a long time and thus remaining persistently exposed to depredation. As grazing cattle are usually not supervised by shepherds or dogs, collars can be the only practical protection tool. Production and sales of collars can become a sustainable small-scale business for farmers to further boost conservation and rural livelihoods.