OBJECTIVE: We aimed to assess the pain perception of preterm infants treated with different surfactant administration techniques by using heart rate variability (HRV). METHODS: Preterm infants who required surfactant therapy for RDS were randomized to INSURE or MIST groups. HRV analysis was performed by Newborn Infant Parasympathetic Evaluation monitor. HRV was recorded before, during and after surfactant administration. Pain assessment was determined by Premature Infant Pain Profile (PIPP) score. RESULTS: Fourteen infants were enrolled in the study. Demographic characteristics of the groups were similar. PIPP scores did not differ between INSURE and MIST groups (p = 0.05). Statistically significant difference in median HRV during surfactant administration was observed between INSURE and MIST groups (52 vs. 56, p = 0.03). HRV analysis was similar between groups before and after surfactant administration. CONCLUSION: Surfactant administration with MIST technique might be more comfortable for preterm infants with RDS. However further studies with larger series are needed.