In patients with heart failure and a maintained ejection fraction, endurance exercise improves peak oxygen consumption (peak Vo2) (HFpEF). However, it’s unclear whether different exercise types have distinct effects. For a study, the researchers sought to determine if high-intensity interval training, moderate continuous training, and guideline-based physical activity guidance have differing impacts on peak Vo2 change in HFpEF patients. A randomized clinical trial was conducted from July 2014 through September 2018 at 5 locations (Berlin, Leipzig, and Munich, Germany; Antwerp, Belgium; and Trondheim, Norway). 180 sedentary patients with chronic, stable HFpEF were selected from 532 screened patients. The results were assessed by core laboratories blinded to the therapy groups, but the patients and employees who conducted the evaluations were not. For 12 months, patients were randomly assigned (1:1:1; n=60) to high-intensity interval training (3*38 minutes per week), moderate continuous training (5*40 minutes per week), or guideline control (1-time guidance on physical activity according to guidelines) (3 months in clinic followed by 9 months telemedical supervised home-based exercise). The primary outcome was a change in peak Vo2 after 3 months, with a clinically significant difference of 2.5 mL/kg/min. After 3 and 12 months, secondary end goals were changes in cardiorespiratory fitness, diastolic function, and natriuretic peptides. 166 (92%) and 154 (86%) of the 180 randomized patients (mean age, 70 years; 120 women [67%]) completed evaluations at 3 and 12 months, respectively. Change in peak Vo2 over 3 months for high-intensity interval training vs guideline control was 1.1 vs 0.6 mL/kg/min (difference, 1.5 [95 % Confidence interval, 0.4 to 2.7]); for moderate continuous training vs guideline control, 1.6 vs 0.6 mL/kg/min (difference, 2.0 [95 % Confidence interval, 0.9 to 3.1]); and for high-intensity interval training vs moderate continuous training, 1.1 vs 1.6 mL/kg/min (difference, −0.4 [95% CI, −1.4 to 0.6]). After a year, no comparisons were statistically significant. Diastolic function and natriuretic peptides did not change significantly. There was no statistically significant difference in peak Vo2 change between those assigned to high-intensity interval vs moderate continuous training at 3 months among patients with HFpEF, and neither group met the prespecified minimal clinically important difference when compared to the guideline control. In comparison to guideline-based physical activity, these data do not support either high-intensity interval training or moderate continuous training for patients with HFpEF.