Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT. Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (n=30) or usual care (UC; n=32). Activity comprised multicomponent exercise training (3 days/week) and sedentary time reduction (≥30 min/day) program and was delivered throughout hospitalization (≈4 weeks) and for 12 weeks after discharge. Physiological assessments conducted before admission and at 12 weeks after discharge included cardiopulmonary exercise testing to quantify peak oxygen uptake ([Formula: see text]), exercise cardiac magnetic resonance imaging for peak cardiac volume (CI_peak) and stroke volume (SVI_peak) index, echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and cardiac biomarkers (cTn-I [troponin-I] and BNP [B-type natriuretic peptide]). Fifty-two participants (84%) completed follow-up (25 activity and 27 UC); median (interquartile range [IQR]) adherence to the activity program was 74% (41-96%). There was a marked decline in [Formula: see text] in the UC program (-3.4 mL‧kg^-1‧min^-1 [95% CI, -4.9 to -1.8]) that was attenuated with activity (-0.9 mL‧kg^-1‧min^-1 [95% CI, -2.5 to 0.8]; interaction <i>P</i>=0.029). Activity preserved exercise cardiac function, with preservation of CI_peak (0.30 L‧min^-1‧m^-² [95% CI, -0.34 to 0.41]) and SVI_peak (0.6 mL/m² [95% CI, -1.3 to 2.5]), both of which declined with UC (CI_peak, -0.68 L‧min^-1‧m^-² [95% CI, -1.3 to -0.32]; interaction <i>P</i>=0.008; SVI_peak, -2.7 mL/m² [95% CI, -4.6 to -0.9]; interaction <i>P=</i>0.014). There were no treatment effects of activity on cardiac biomarkers or echocardiographic indices. Multicomponent activity intervention during and after allo-SCT is beneficial for preserving patient cardiorespiratory fitness and exercise cardiac function. These results may have important implications for cardiovascular morbidity and mortality after allo-SCT. URL: https://anzctr.org.au/; Unique identifier: ACTRN12619000741189.