Abstract Less invasive surfactant administration (LISA) has become increasingly popular in neonatal intensive care units (NICUs), but there are currently no guidelines for the premedication prior to this procedure. The aim of this observational study was to compare the efficacy and tolerance of intravenous administrations of ketamine and propofol before LISA in neonates born before 30 weeks of gestational age (GA). The primary outcome was requirement of intubation within 2 h of the procedure.