AIMS: This study aimed to explore effects of exergaming and medical yoga on exercise capacity, fatigue, shortness of breath, health-related quality of life, depression, and anxiety in patients with heart failure. METHODS AND RESULTS: A randomized sub-study with a 3-month intervention and outcomes measures at baseline, 3, 6, and 12 months. Participants were recruited from heart failure clinics in Sweden. Treatment effects in change of outcomes were tested in an analysis of mixed-effects models with repeated measures. Change in outcomes was the dependent variable. The independent fixed-effect parameters were treatment group, time, and the interaction between treatment group and time.In total, 104 patients (37% women, mean age 71 ± 12, 48% in New York Heart Association Class II and 42% in III) were randomized to exergaming (n = 35), medical yoga (n = 33), or an active control group (n = 36). No statistically significant differences were found between these three groups on any of the outcome measures. Exergaming significantly improved exercise capacity, fatigue, shortness of breath, and physical health-related quality of life and medical yoga improved symptoms of fatigue and emotional health-related quality of life. The control group did not change on the exercise capacity, symptoms, health-related quality of life, or depressive or anxiety symptoms. The well-being score in patients in the control group significantly decreased at 3 months. CONCLUSION: Both exergaming and medical yoga demonstrated positive impacts on outcomes when compared with a control group. Exergaming, characterized by its elevated physical intensity, exerted effects primarily on physical health, while medical yoga, as a mind-body intervention, exhibited influences on emotional well-being. REGISTRATION: ClinicalTrial.gov: NCT01785121.