Sustainable wildlife management is necessary to guarantee the viability of source populations; but it is rarely practiced in the tropics. The yellow anaconda (Eunectes notaeus) has long been harvested for its leather. Since 2002 its harvest has operated under a management program in northeastern Argentina, which relies on adaptive management practices, that limit the minimum body length permitted for harvesting, the number of active hunters and the length of hunting seasons. Here we investigated the effects of yellow anaconda harvest on its demography based on 2002–2019 data and show that exploitation levels are sustainable. The gradual reduction in annual hunting effort, due to a decrease in the number of hunters and hunting season duration, reduced the total number of anacondas harvested. Conversely, captures per unit effort increased across the study period. The body size of anacondas was not influenced by the harvesting, and more females than males were caught. We also found that a decrease in mean temperature positively influenced anaconda harvest and the capture of giant individuals. Because sustainable use is a powerful tool for conservation, and anacondas are widespread in South America, these discoveries are highly applicable to other species and regions.