The effects of high-intensity interval training (HIIT) on dyspnea and aerobic fitness in adults with asthma are poorly understood. To compare constant-load exercise (CLE) versus HIIT for improvements in dyspnea symptoms and clinical control in adults with moderate-to-severe asthma. Participants were randomized into 2 groups: CLE (n = 27; started with 70% of maximal watts [Wmax] obtained during cardiopulmonary exercise testing [CPET]) and HIIT (n = 28; started with 80% and increased until 140% Wmax). Exercise training lasted 12 weeks (twice/week, 40 minutes/session on a cycle ergometer), and the intensity was based on CPET. Clinical asthma control (Asthma Control Questionnaire), aerobic fitness (the peak of oxygen uptake), health-related quality of life (Asthma Quality of Life Questionnaire), physical activity levels (PAL; accelerometer), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale questionnaire), and dyspnea were evaluated before and after the intervention. Systemic and airway inflammation were also assessed. Two-way analysis of variance and χ2 tests were used for comparisons. Sixteen participants dropped out during the interventions and returned for the final evaluations. The CLE and HIIT groups showed similar improvements in aerobic fitness. The HIIT group had lower dyspnea and fatigue perception scores and higher PAL than the CLE group (P < .05) and clinical improvements in the psychosocial distress. In addition, only the HIIT group achieved a minimal clinically important difference in asthma symptoms. There was no change in the systemic and airway inflammation (P > .05). Both interventions promoted similar improvements in aerobic fitness; however, HIIT induced a greater reduction in dyspnea and fatigue perception. Similar responses were observed for other variables.