OBJECTIVE: To determine the cost-effectiveness of the World Health Organization (WHO) Essential Newborn Care (ENC) training of health care providers in first-level facilities in the 2 largest cities in Zambia. METHODS: Data were extracted from a study in which the effectiveness of the ENC training was evaluated (including universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, skin-to-skin care, care of the small infant, danger signs, and common illnesses). The costs to train an ENC instructor for each first-level delivery facility and the costs of salary/benefits for 2 coordinators responsible for maintenance of the program were recorded in 2005 US dollars. The incremental costs per life gained and per disability-adjusted life-year averted were calculated. SETTING: A 5-day ENC training-of-trainers was conducted in Lusaka, Zambia, to certify 18 college-trained midwives as ENC instructors. The instructors trained all clinic midwives working in their first-level facilities as part of a before-and-after study of the effect of ENC training on early neonatal mortality conducted from Oct 2004 to Nov 2006. RESULTS: All-cause 7-day (early) neonatal mortality decreased from 11.5 per 1000 to 6.8 per 1000 live births after ENC training of the clinic midwives (relative risk: 0.59; 95% confidence interval: 0.48-0.77; P < .001; 40 615 births). The intervention costs were $208 per life saved and $5.24 per disability-adjusted life-year averted. CONCLUSIONS: ENC training of clinic midwives who provide care in low-risk facilities is a low-cost intervention that can reduce early neonatal mortality in these settings. Copyright © 2011 by the American Academy of Pediatrics.