Purpose: In this study, we compared the efficacy of the RAM cannula and the short binasal prong (SBP) as noninvasive ventilation (NIV) interfaces in preterm infants with respiratory distress syndrome (RDS). Materials and Methods: Premature infants with RDS who required NIV were randomized in the RAM cannula and SBP groups within the first half hour. The groups were compared in terms of their need for invasive ventilation, their surfactant use, and their morbidities. Results: We assessed 126 patients (62 SBPs and 64 RAM cannulas). Clinical and demographic features of the groups were similar. Within the first 72 hours, the RAM cannula group showed a higher need for invasive ventilation (32.8 and 9.6%, p = .002, respectively), surfactant (42.1 and 19.3%, p = .007, respectively), and rate of pulmonary hemorrhage was also higher. There were no differences between the groups in terms of other morbidities. Conclusions: In preterm infants with RDS, RAM cannula use as an interface for NIV results in increased invasive ventilation and surfactant use.