Hematopoietic cell transplantation (HCT) is a life-saving treatment for patients with high-risk hematological malignancies. Prognostic measures to determine fitness for HCT are needed to inform decision-making and interventions. VO(2peak) is obtained by measuring gas exchange during cycle ergometry and has not been studied as a prognostic factor in HCT. Thirty-two autologous and allogeneic HCT patients underwent VO(2peak) and 6 Minute Walk (6MW) testing before HCT, and provided weekly symptom and health-related quality of life (HRQOL) assessments before HCT and concluding at Day 100. Twenty-nine patients completed pre-HCT testing. Pre-HCT VO(2peak) was positively correlated with pre-HCT 6MW (r=0.65, P<0.001) and negatively correlated with number of chemotherapy regimens and months of chemotherapy. Patients with lower VO(2peak) reported higher symptom burden and inferior HRQOL at baseline and during early post-HCT period. Patients with pre-HCT VO(2peak) <16 mL/kg/min had higher risk of mortality post HCT (entire cohort: hazard ratio (HR) 9.1 (1.75-47.0), P=0.01; allogeneic HCT patients only: HR 6.70 (1.29-34.75), P=0.02) and more hospitalized days before Day 100 (entire cohort: median 33 vs 19, P=0.003; allogeneic HCT patients only: median 33 vs 21, P=0.004). VO(2peak) pre-HCT is feasible and might predict symptom severity, HRQOL and mortality. Additional studies are warranted.