Objective: To determine the validity and reproducibility of heart rate (HR) and crutch force measurements to estimate energy expenditure during paraplegic walking. Usefulness of these outcome measures in comparative trials was assessed in terms of responsiveness. Design: Cross-sectional validity was determined using one single (first) measurement. Longitudinal validity as well as reproducibility were calculated using repeated measurements. Setting: Oxygen uptake and HR during steady state as well as axial crutch load were measured at subjects' self-selected walking speeds. Patients: Ten subjects with thoracic-level spinal cord injury were included in the study. All subjects had considerable experience with ambulation in the advanced reciprocating gait orthosis (ARGO). Main Outcome Measures: Oxygen uptake ( O2, mL/min) and oxygen cost (Eo2, mL/m) were used as criterion standards. Crutch peak force (CPF), crutch force time integral (CFTI), HR, and physiological cost index (PCI) were used to estimate energy expenditure. Results: The PCI was found to be sensitive to detect differences between sessions in criterion standard (r = .86). Smallest detectable difference (ie, point where difference exceeds measurement error) ranged from approximately 15% for CPF to 33.7% and 41.8% for Eo2 and PCI, respectively. Conclusions: Although PCI is expected to be a valid measure for within-patient differences in O2, responsiveness was lower compared to Eo2 and CPR. The limited number of patients who can be included in studies on paraplegic locomotion requires reproducible outcome measures. Therefore, CPF and Eo2 are advocated in favor of PCI.