BACKGROUND: In high-income countries, administration of antenatal steroids is standard care for women with anticipated preterm labour. However, although >1 million deaths due to preterm birth occur annually, antenatal steroids are not routine practice in low-income countries where most of these deaths occur. OBJECTIVES: To review the evidence for and estimate the effect on cause-specific neonatal mortality of administration of antenatal steroids to women with anticipated preterm labour, with additional analysis for the effect in low- and middle-income countries. METHODS: We conducted systematic reviews using standardized abstraction forms. Quality of evidence was assessed using an adapted GRADE approach. Existing meta-analyses were reviewed for relevance to low/middle-income countries, and new meta-analysis was performed. RESULTS: We identified 44 studies, including 18 randomised control trials (RCTs) (14 in high-income countries) in a Cochrane meta-analysis, which suggested that antenatal steroids decrease neonatal mortality among preterm infants (<36 weeks gestation) by 31% [relative risk (RR) = 0.69; 95% confidence interval (CI) 0.58-0.81]. Our new meta-analysis of four RCTs from middle-income countries suggests 53% mortality reduction (RR = 0.47; 95% CI 0.35-0.64) and 37% morbidity reduction (RR = 0.63; 95% CI 0.49-0.81). Observational study mortality data were consistent. The control group in these equivalent studies was routine care (ventilation and, in many cases, surfactant). In low-income countries, many preterm babies currently receive little or no medical care. It is plausible that antenatal steroids may be of even greater effect when tested in these settings. CONCLUSIONS: Based on high-grade evidence, antenatal steroid therapy is very effective in preventing neonatal mortality and morbidity, yet remains at low coverage in low/middle-income countries. If fully scaled up, this intervention could save up to 500 000 neonatal lives annually.