Rationale: Aerosolized albuterol is widely used, but its safety and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established. Objectives: To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD. Methods: Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25mg, 2.5mg) and 3ml of normal saline were administered every 4 hours during separate 24-hour treatment periods assigned in random order with a 6-hour washout phase between periods. The primary outcome was the absolute change (post–pre therapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia. Results: Average within subject EF75 values improved with each therapy: saline placebo (+0.45L/min  2.5, p=0.04), 1.25mg of albuterol (+0.70L/min  2.4, p<0.001), and 2.5mg of albuterol (+0.38L/min  2.4, p=0.06). However, 1.25mg of albuterol (0.26L/min; 95% CI -0.19, 0.72) and 2.5mg (-0.10L/min; 95% CI -0.77, 0.57) produced similar changes in EF75 when compared to saline. All secondary outcomes were similar between saline and 1.25mg of albuterol. Peak inspiratory pressure needed to deliver goal tidal volumes (7.5% relative decrease, 95% CI 2.6, 12.3) and heart rate (6.5% increase, 95% CI 2.2, 10.8) differed significantly between albuterol 2.5mg and saline. Conclusion: Albuterol at 1.25mg and 2.5mg, compared to aerosolized saline, did not affect EF75 in infants with sBPD receiving invasive ventilation. Greater improvement in inspiratory pressures with albuterol 2.5mg suggests benefit, but close heart monitoring is indicated.