In the past 5 years, the time-lapse culture system (TLS) has gradually been applied to the field of assisted reproduction. However, there are few reports on the comparison between this system and the conventional culture system (CS) on the outcome of newborns. As a new model in embryo culture, we should pay attention to its neonatal outcomes. We examined 15,252 fresh transfer cycles processed between January 2016 and December 2019. After propensity score matching, embryos in two groups, TLS and CS, had similar rates of miscarriages, ectopic pregnancy, and live delivery (P > 0.05). Embryos in the TLS group achieved higher clinical pregnancy and implantation rates (P < 0.05). Of the perinatal and neonatal outcomes, singletons and twins were analyzed separately. No significant differences were observed in gestational age, preterm deliveries, birth weight, and sex ratio (P > 0.05). Incidences of malformations of babies delivered from CS and TLS groups were also similar between the two groups. Embryos cultured in a TLS are as safe as CS with regard to neonatal outcomes, including congenital malformations.© 2021. Society for Reproductive Investigation.