BACKGROUND: Patients with heart failure experience not only impaired physical condition, but also their physical activity, moods, and quality of life may be diminished. AIMS: The purpose of this study was to investigate the effects of 12-week walking with breathing program on physical activity tolerance considering time-dependent physiological factors and time-independent interoceptive awareness, as well as psychosocial factors. METHODS: This randomized controlled trial recruited 90 heart failure patients and randomly assigned them. The walking with breathing group received the walking and breathing intervention for 12 weeks but the control group did not. Outcomes included activity tolerance measured by 6-minute walk distance, moods assessed by the Hospital Anxiety and Depression Scale, quality of life determined by the EuroQol 5-Dimensions, oxygen saturation by pulse oximetry, and interoceptive awareness by the Multidimensional Assessment of Interoceptive Awareness scale. Data were collected before the intervention at baseline and at Weeks 2, 4 and 12. RESULTS: The results of the generalized estimating equation showed the 6-minute walk distance in the walking with breathing group was significantly different across time ( p<0.001) compared with the control group at baseline. Oxygen saturation by pulse oximetry ( p=0.04) and Trusting on the Multidimensional Assessment of Interoceptive Awareness scale ( p=0.001) significantly and positively correlated with results of the 6-minute walk distance. There were significant between-group differences at Week 12 in anxiety ( p=0.03) and quality of life ( p=0.02) but not depression ( p=0.06). CONCLUSIONS: Walking with breathing improved heart failure patients' tolerance of physical activity, probably because of improved oxygen saturation and trusting interoceptive awareness. Walking with breathing also improved patients' anxiety and quality of life.