Predation by jaguars (Panthera onca) and pumas (Puma concolor) is often a source of conflict with cattle ranching in northeastern Sonora, Mexico. Because jaguars are endangered in Mexico, such conflicts have biological, social, and economic consequences. We documented the extent of predation by jaguars and pumas on cattle in 1999–2004 in northeastern Sonora, where the northernmost breeding population of jaguars exists in North America. Jaguars and pumas killed only calves < 12 mo old, and calves constituted 58% of prey biomass consumed by jaguars and 9% by pumas. Annual cause-specific mortality rates of confirmed jaguar predation (≤ 0.018), confirmed and suspected jaguar predation (≤ 0.018), and all confirmed and suspected large felid predation (≤ 0.018) were low and cattle calf survival was high (0.89–0.98 annually). If calves reported as missing but for which no evidence of mortality could be found were classed as large felid predation, annual cause-specific rates increased to 0.006–0.038. Collectively, confirmed jaguar and puma predation accounted for < 14% (57/408) of total cattle losses, with jaguars responsible for 14% of all calf losses; this could increase to a maximum of 36% (146/408) if missing calves were included in the totals. While jaguar and puma predation may have an impact on some small cattle operations, it is generally minor compared to losses from other causes in northeastern Sonora. Moreover, 91% of all confirmed calf kills were associated with three individual jaguars in our study. Targeting problem cats rather than broad-scale predator control may therefore be a viable alternative to address chronic predation problems. Because most (83%) instances of jaguar predation occurred during the dry season along thick riparian habitats, modified cattle husbandry operations, such as establishment of permanent water sources in uplands and away from dense vegetative cover, could ameliorate many cases of predation by jaguars on cattle.