Abstract. Background: In preterm infants at risk for RDS, reintubation following surfactant replacement therapy and successful extubation may be associated with poor clinical outcomes. Methods: Initial extubation, reintubation, mortality, and major morbidity rates associated with prematurity from two surfactant trials utilizing lucinactant, colfosceril palmitate, beractant, and poractant alfa were compared for reintubated infants versus infants who were not reintubated, and among treatment groups. Results: Initial extubation rates were similar among surfactant treatments in both trials (80–84%; p=ns). Reintubated infants had significantly higher mortality rates versus infants who were successfully extubated and never reintubated (18% vs. 0.5% respectively; OR 42 [CI 15.1–114]). Reintubated infants also had higher rates of BPD (OR 8.2; CI 5.8–11.5), air leak (3.0; 2.1–4.5), sepsis (3.6; 2.6–4.9), NEC (2.6; 1.8–3.7), IVH (3.3; 2.4–4.5), and PVL (1.8; 1.1–2.8). Reintubation rates were lower (p < 0.05) and combined outcomes of survival without reintubation were higher for infants treated with lucinactant versus beractant or poractant alfa (p < 0.05). Conclusions: Reintubation following surfactant therapy and extubation in preterm infants at risk of RDS is associated with higher morbidity and mortality. There appear to be differences in reintubation rates and survival without reintubation between surfactant preparations, with no differences in other complications of prematurity.