Background: From 2010 through 2013, integrated health and environmental responses addressed an unprecedented epidemic lead poisoning in Zamfara State, northern Nigeria. Artisanal gold mining caused widespread contamination resulting in the deaths of > 400 children. Socioeconomic, logistic, and security challenges required remediation and medical protocols within the context of local resources, labor practices, and cultural traditions. Objectives: Our aim was to implement emergency environmental remediation to abate exposures to 17,000 lead poisoned villagers, to facilitate chelation treatment of children ≤ 5 years old, and to establish local technical capacity and lead health advocacy programs to prevent future disasters. Methods: U.S. hazardous waste removal protocols were modified to accommodate local agricultural practices. Remediation was conducted over 4 years in three phases, progressing from an emergency response by international personnel to comprehensive cleanup funded and accomplished by the Nigerian government. Results: More than 27,000 m³ of contaminated soils and mining waste were removed from 820 residences and ore processing areas in eight villages, largely by hand labor, and disposed in constructed landfills. Excavated areas were capped with clean soils (≤ 25 mg/kg lead), decreasing soil lead concentrations by 89%, and 2,349 children received chelation treatment. Pre-chelation geometric mean blood lead levels for children ≤ 5 years old decreased from 149 μg/dL to 15 μg/dL over the 4-year remedial program. Conclusions: The unprecedented outbreak and response demonstrate that, given sufficient political will and modest investment, the world’s most challenging environmental health crises can be addressed by adapting proven response protocols to the capabilities of host countries. Citation: Tirima S, Bartrem C, von Lindern I, von Braun M, Lind D, Anka SM, Abdullahi A. 2016. Environmental remediation to address childhood lead poisoning epidemic due to artisanal gold mining in Zamfara, Nigeria. Environ Health Perspect 124:1471–1478; http://dx.doi. org/10.1289/ehp.1510145