Antenatal corticosteroids (ACS) during preterm labour reduce neonatal mortality and morbidity. Evidence on preterm multiple pregnancies is limited and contradictory. Compare the effect of ACS on very low birth weight infant's (VLBW) mortality and morbidity among singleton and multiple pregnancies. Retrospective cohort study, employing prospectively collected data, of infants 23 to 34 weeks' gestation and 500 to 1500 g born at the Neocosur Neonatal Network centers during 2007–2016. Neonatal outcomes were compared among singleton and multiple pregnancies exposed to at least one dose of ACS to those not exposed using logistic regression analyses controlled for birthweight, gestational age, sex, small for gestational age (SGA) and mode of delivery. A total of 13,864 infants were studied; 2948 multiple (21.3%) and 10,904 singleton pregnancies (78.7%). Overall, 11,218 (81.4%) received at least one dose of ACS with a significant reduction in the risk of death, RDS and grade III or IV IVH compared to those not exposed. Both singleton and multiple pregnancies exposed to ACS showed similar reduced risk of death (aRR 0.41 95% CI, 0.36–0.47 vs. aRR 0.46 95% CI, 0.34–0.64). However, ACS were not associated with reduced odds of RDS (aRR 0.89 95% CI, 0.66–1.23) or grade III or IV IVH (aRR 0.99 95% CI, 0.67–1.48) in multiple pregnancies. The benefit of administration of at least one dose of ACS in VLBW multiple and singleton pregnancies is comparable in terms of death. However, ACS showed no relevant impact in short-term morbidity in multiple pregnancies. •The benefit of at least one dose of ACS in VLBW multiple and singleton pregnancies is comparable in terms of death.•ACS are not associated with a reduction in the rates of RDS, HIV, NEC or ROP in multiple pregnancies.•Further research is urgently needed to fully understand the effects of ACS in multiple pregnancies.