Rationale: Moderate to severe asthma is associated with impaired asthma control and quality of life (QoL) despite access to specialist care and modern pharmacotherapy. Breathing exercises (BrEX) improve QoL in incompletely controlled mild asthma, but impact in moderate to severe asthma is unknown. Objectives: To investigate the effectiveness of BrEX as adjuvant treatment on QoL in patients with uncontrolled moderate to severe asthma. Methods: Adult patients with incompletely controlled asthma attending respiratory specialist clinics were randomized to usual specialist care (UC) or UC and BrEX (UC 1 BrEX) with three individual physiotherapist-delivered sessions and home exercises. Primary outcome was asthma-related QoL (Mini-Asthma Quality of Life Questionnaire [Mini-AQLQ]) at 6 months on the basis of intention-to-treat analysis. Secondary outcomes: Mini-AQLQ at 12 months, lung function, 6-minute-walk test, physical activity level, Nijmegen Questionnaire, Hospital Anxiety and Depression Scale, and adverse events. Repeated-measures mixed-effects models were used to analyze data. Poisson regression models were used to analyze adverse event incidence rate ratio. Results: A total of 193 participants were allocated to UC 1 BrEX (n = 94) or UC (n = 99). UC 1 BrEX was superior in the primary outcome (adjusted mean change difference, 0.35; 95% confidence interval [CI], 0.07 to 0.62). Superiority in Mini-AQLQ was sustained at 12 months (0.38; 95% CI, 0.12 to 0.65). A minor improvement in Hospital Anxiety and Depression Scale depression score at 6 months favoring UC 1 BrEX (20.90; 95% CI, 21.67 to 20.14) was observed. Asthma-related adverse events occurred similarly in UC 1 BrEX and UC participants: 14.9% versus 18.1% (P = 0.38). Conclusions: BrEX as add-on to usual care improve asthma-related QoL in incompletely controlled asthma regardless of severity and with no evidence of harm.