Background: Bronchial thermoplasty is designed to reduce airway smooth muscle and improve asthma control. This study was conducted to determine the safety and efficacy of this procedure in subjects with symptomatic, severe asthma. Methods: Adults symptomatic despite treatment with fluticasone or equivalent at >750 µg /day, a long-acting ₂-agonist, and other medication which could include 30mg oral prednisolone/day were randomized to bronchial thermoplasty (BT) or to Control. Following treatment, subjects entered a 16-week Steroid Stable Phase (Weeks 6-22), a 14-week Steroid Wean Phase (Weeks 22-36), and a 16-week Reduced Steroid Phase (Weeks 36-52). Results: Bronchial thermoplasty resulted in a transient worsening of asthma symptoms. Seven hospitalizations for respiratory symptoms occurred in 4 out of 15 BT subjects during the Treatment Period. Five hospitalizations were within 3 days of treatment. Two subjects had segmental collapse involving the most recently treated lobe; 1 required bronchoscopy and aspiration of a mucus plug. There were no hospitalizations during this period in the 17 Control subjects. The rate of hospitalizations was similar in both groups in the Post-Treatment Period. At 22 weeks, BT subjects had significant improvements versus Control subjects in rescue medication use (-26.6±40.1 vs. - 1.5±11.7 puffs/7 days, p<0.05), pre-bronchodilator FEV₁ %predicted (14.9±17.4 vs. - 0.94±22.3, p=0.04), and Asthma Control Questionnaire (ACQ) scores (-1.04±1.03 vs. - 0.13±1.00, p=0.02). Improvements in rescue medication use and ACQ remained significantly different from Control at 52 weeks. Interpretation: Bronchial thermoplasty is associated with a short-term increase in asthma-related morbidity. However, there is preliminary evidence of long-lasting improvement in asthma control. Registered at www.clinicaltrials.gov, ID# NCT00214539