Refractory pneumothoraces with bronchopleural fistula (BPF) pose a significant challenge in managing critically sick and ventilated neonates. We report a case of the term female neonate being treated with extracorporeal membrane oxygenation (ECMO) support for meconium aspiration and presumed sepsis, with a significant air leak refractory to pleural drainage that was managed using endobronchial application of cyanoacrylate (enbucrilate) glue to seal the leak.