Surfactant replacement therapy through the endotracheal tube has been shown to improve lung compliance and reduce pulmonary pressures. Minimally invasive surfactant therapy (MIST) combines the benefits of continuous positive airway pressure (CPAP) and surfactant for spontaneously breathing preterm infants. We aimed to characterize the haemodynamic changes accompanying the first dose of MIST in preterm infants.Poractant alfa (200 mg/kg) was administered as MIST while on CPAP support. Echocardiograms were performed before (T1) and 30 (T2) and 60 min (T3) after MIST to assess serial change.Twenty infants (mean gestational age 29.5 ± 2.8 weeks, median birth weight 1,102 g, IQR 840-1,940) received MIST at a median age of 16 h (IQR 3-24). FiO2 decreased significantly at 30 min (0.41 ± 0.08 to 0.27 ± 0.03, p < 0.001). Significant changes were noted at T2 for ductal parameters (decreased % time right to left shunt: 25% [15-33] to 14.5% [6-22], p = 0.013). Reduced pulmonary vascular resistance (PVR; increased pulmonary artery time velocity ratio 0.23 ± 0.05 to 0.28 ± 0.04 ms, p = 0.004) and improved longitudinal (tricuspid annular plane systolic excursion 4.5 ± 0.8 to 5.3 ± 0.9 mm, p = 0.004) and global (fractional area change 25 ± 2.3 vs. 27 ± 2%, p = 0.002) ventricular function were noted.This is the first study assessing cardiovascular adaptation to MIST, a procedure fast gaining acceptance in the neonatal community. Increased pulmonary blood flow is likely due to a combined effect of increased ductal flow, reduced PVR, and increased ventricular function.