The aim of this randomized, double-blind pilot study was to evaluate the short-term efficacy of early inhalation therapy with budesonide in ventilator-dependent preterm infants. The primary outcome variable was the duration of artificial ventilation; secondary outcome variables were the need for supplemental oxygen and the release of several inflammatory mediators in the tracheobronchial aspirate fluid. The infants of the budesonide group could not be weaned earlier from the ventilator. The ventilatory parameters on day 14 of life and the need for supplemental oxygen were similar in both groups. The release of inflammatory mediators was not reduced in the budesonide group. No adverse side effects were observed in either group. In conclusion, aerosolized budesonide failed to demonstrate significant short-term pulmonary improvement in ventilator-dependent preterm infants.