Objective This study compared the clinical features, cardiac structure and function evaluated by echocardiography, cardiopulmonary response to exercise and long-Term clinical outcomes between patients with heart failure (HF) induced by cancer therapy (CTHF) and heart failure not induced by cancer therapy (NCTHF). Methods We evaluated 75 patients with CTHF and 894 with NCTHF who underwent clinically indicated cardiopulmonary exercise testing, and followed these individuals for a median of 4.5 (3.0-5.8) years, during which 187 deaths and 256 composite events (death, heart transplantation and left ventricular (LV) assistant device implantation) occurred. Results Compared with NCTHF, patients with CTHF were younger, with lower prevalence of cardiovascular comorbidities, higher LV ejection fraction (LVEF), but similar global longitudinal strain. LV diastolic function (higher E/e′ ratio) and compliance (higher end-diastolic pressure/LV end-diastolic volume index ratio) were worse in CTHF and were both associated with adverse outcomes. Despite a favourable clinical profile, peak VO 2 and VE/VCO 2 slope were similarly impaired in CTHF and NCTHF. In multivariable Cox regression analysis including clinical characteristics, cardiopulmonary exercise testing variables and LVEF, CTHF was associated with a significantly higher risk of death (HR 2.64; 95% CI 1.53 to 4.55; p=0.001) and composite events (HR 1.79; 95% CI 1.10 to 2.91; p=0.019) compared with NCTHF. Conclusions CTHF is characterised by a distinct clinical profile, better LVEF but worse LV diastolic properties, and similarly impaired global longitudinal strain, functional capacity and ventilatory efficiency. Accounting for differences in clinical characteristics, CTHF was associated with worse long-Term prognosis than NCTHF.