In Africa, HIV and feeding practices deeply affect child mortality. To prevent mother-to-child transmission, the World Health Organization recommends exclusive breastfeeding for 6 months and replacement feeding when acceptable, feasible, affordable, and sustainable. Determining the proportion and number of children saved with exclusive breastfeeding and replacement feeding is essential to design and implement crucial nationwide policies. Using data on 31 sub-Saharan countries and a decision tree for risk assessment, the authors estimated the number of children's lives potentially saved according to 6 scenarios that combine exclusive breastfeeding for 6 months or replacement feeding with 3 promotion strategies. Among all HIV-negative children born to HIV-positive mothers who die in sub-Saharan Africa per year, 52,315 (9.6%) would be saved yearly with exclusive breastfeeding versus 21,638 (4.0%) with replacement feeding. Promotion support would double these numbers (110,625 vs 45,330; ie, 20.3% vs 8.3%), and with additional prenatal group education, 132,633 versus 54,192 lives would be saved (24.3% vs 9.9%). Wherever replacement feeding is not possible, exclusive breastfeeding with promotion support and prenatal group education would save 1 of 4 exposed children.