Background In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life. Methods Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 – December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 – May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association. Results All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity. Conclusion The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA.