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Objective: Bronchial thermoplasty (BT) as an add-on therapy for uncontrolled severe asthma is an alternative to biologic therapies like omalizumab (OM). We conducted an indirect treatment comparison (ITC) to appraise comparative effectiveness of BT and OM., Methods: A systematic literature review identified relevant randomized controlled trials. The ITC followed accepted methodology., Results: The ITC comprised a sham-controlled trial of BT (AIR2) and two placebo-controlled trials of OM (INNOVATE; EXTRA). Comparing the BT post-treatment period to ongoing treatment with OM, showed no significant differences in the rate ratios (RRs) for severe exacerbations (RR of BT versus OM = 0.91 [95% CI: 0.64, 1.30]; p = 0.62) or hospitalizations (RR = 0.57 [95% CI: 0.17, 1.86]; p = 0.53); emergency department visits were significantly reduced by 75% with BT (RR = 0.25 [95% CI: 0.07, 0.91]; p = 0.04); the proportions of patients with clinically meaningful response on the asthma quality-of-life questionnaire were comparable (RR = 1.06 [95% CI: 0.86, 1.34]; p = 0.59). The RR for exacerbations statistically favours OM over the total study period in AIR2 (RR = 1.50 [95% CI: 1.11, 2.02]; p = 0.009) likely reflecting a transient increase in events during the BT peri-treatment period., Conclusions: The ITC should be interpreted cautiously considering the differences between patient populations in the included trials. However, based on the analysis, BT compares well with a potentially more costly pharmacotherapy for asthma. Clinicians evaluating the relative merits of using these treatments should consider the totality of evidence and patient preferences to make an informed decision.