RATIONALE: There is considerable variability in patient outcomes following bronchial thermoplasty (BT), an adjunct therapy for patients with severe asthma. It is unclear if the presence of airway inflammation is important to consider prior to BT. OBJECTIVE: The objective of the article was to ascertain if optimizing airway inflammation guided by sputum cell counts prior to BT, as compared to guideline-based-care, results in better patient outcomes and improved airway hyperresponsiveness. METHODS: We retrospectively evaluated asthmatics who underwent BT at our institution (Firestone Institute for Respiratory Health, St. Joseph’s Healthcare Hamilton, Canada) and compared clinical outcomes (asthma-quality-of-life-questionnaire [AQLQ], asthma-control-questionnaire [ACQ] and provocative concentration of methacholine required to decrease the forced expiratory volume in one second by 20% [PC20]) in those patients managed using guideline-based-care (n = 7) versus a protocol that involved optimizing airway inflammation using quantitative sputum cell counts (n = 7). MEASUREMENTS AND MAIN RESULTS: Following BT, there were greater improvements in the inflammation-optimized group than in the guideline-based-care group for the asthma-quality-of-life-questionnaire (ΔAQLQ: 2.2 ± 1.2 vs 0.8 ± 0.9, p = 0.04), asthma-control-questionnaire (ΔACQ: −2.3 ± 1.3 vs −0.5 ± 1.1, p = 0.02) and airway hyperresponsiveness (ΔPC20: 3.9 ± 1.2 vs. 0.6 ± 0.8 doubling-doses, p = 0.008). CONCLUSION: This is the first study to provide preliminary evidence that BT, when performed after normalizing sputum cell counts, significantly improves patient reported outcomes and airway hyperresponsiveness, compared to current guidelines that presume airway inflammation is controlled.