Objective: To determine whether early polyethylene bag use with skin-to-skin care compared with skin-to skin care alone reduce hypothermia among infants born at term in resource-limited settings. Study design: Infants born at term in the tertiary referral center in Lusaka, Zambia, were randomized using sequentially numbered sealed opaque envelopes in 2 phases: after birth (phase 1) and at 1 hour after birth (phase 2) to either skin-to-skin care with polyethylene bags or skin-to-skin care alone. Infant and maternal temperatures were recorded at birth, 1 hour, and every 4 hours until discharge or 24 hours. Results: We enrolled 423 infants from May 2017 to August 2017. The rate of moderate-severe hypothermia (temperature <36.0°C) at 1 hour was 72 of 208 (34.6%) in the skin-to-skin care with a polyethylene bag group compared with 101 of 213 (47.4%) in the skin-to-skin care alone group (relative risk, 0.71; 95% CI 0.56-0.90; P < .01; number needed to treat = 8). phase 1 treatment assignment significantly modified the effect of phase 2 treatment (P = .02 for interaction effect). Among infants randomized to skin-to-skin care with a polyethylene bag in phase 1, the risk of moderate-severe hypothermia was decreased in infants randomized to continue this intervention until discharge compared with infants randomized to skin-to-skin care alone. The rates of severe hypothermia, hyperthermia, and other adverse events did not differ significantly between groups. Conclusions: Low-cost polyethylene bags started after birth in combination with skin-to-skin care reduced moderate or severe hypothermia at 1 hour and at discharge among infants born at term in a resource-limited setting compared with skin-to-skin care alone. Trial Registration: ClinicalTrials.gov: NCT03141723.