Rationale: Bronchial thermoplasty aims to improve asthma symptoms by reducing central airway smooth muscle mass. Up to now, the reduction of smooth muscle mass has been documented only for 1 group of 10 patients who had ≥15% of pre-treatment total bronchial biopsy area occupied by smooth muscle. Objectives: To evaluate the effects of bronchial thermoplasty on airway smooth muscle mass and airway collagen deposition in adult patients with asthma, regardless of pre-treatment smooth muscle area. Methods: Seventeen asthmatics underwent bronchial thermoplasty in 3 visits. At visit 1, bronchial biopsies were taken from the lower lobe that was not treated during this session. At visit 2 (3-14 weeks after the 1st visit), all 17 patients underwent biopsy of the lower lobe treated during the first procedure. At visit 3 (7-22 weeks after the 1st visit), 9 patients agreed to undergo biopsy of the same lower lobe. Histology and immunohistochemistry analyses were performed on the biopsy specimens. Measurements and Main Results: Bronchial thermoplasty decreased airway smooth muscle from 12.9 ± 1.2% of the total biopsy surface at visit 1 to 4.6 ± 0.8% at visit 2 (p < 0.0001). For the 9 patients who underwent a 3rd biopsy, mean airway smooth muscle was 5.3 ± 1.3% at visit 3 (p = 0.0008 compared to baseline). Bronchial thermoplasty also decreased type-1 collagen deposition underneath basement membrane from 6.8 ± 0.3 µm at visit 1 to 4.3 ± 0.2 µm at visit 2 (p <0.0001), and to 4.4 ± 0.4 µm for 9 patients at visit 3 (p < 0.0001 compared to baseline). Over 1 year after treatment, doses of inhaled corticosteroid, the number of severe exacerbations, and asthma control all improved (p ≤ 0.02). Conclusions: For patients with severe asthma, bronchial thermoplasty reduced the smooth muscle mass of treated airway segments regardless of the baseline level of muscle mass. Treatment also altered the deposition of collagen. At follow-up, bronchial thermoplasty improved asthma control; however, the limited number of subjects did not allow to evaluate possible correlations between these improvements and the studied histological parameters. Further studies are needed to confirm these results and evaluate their persistence.