Abstract-Chest optimization, an evidence-based protocolguided multimodal chest physiotherapy consisting of body positioning, sputum mobilization, bronchodilation, and lung hyperinflation, may be routinely administered to ventilatordependent patients with low cervical spinal cord injury (CSCI) for improving pulmonary functional outcomes that facilitate weaning from mechanical ventilation. We undertook this study to determine whether position-specific chest optimization was associated with changes in spontaneous breathing trial (SBT) duration. Cardiac output (CO), alveolar minute volume (MValv), carbon dioxide elimination (VCO 2 ), and static chest compliance (Cst) were measured during chest optimization; then MValv and rapid shallow breathing index (RSBI) were measured during SBT. Study participants (N = 12) were clinically stable ventilator-dependent patients with low CSCI. Trendelenburg chest optimization (TCO) was associated with significant increases in SBT (p < 0.001), CO (p < 0.001), MValv (p < 0.003), VCO 2 (p < 0.001), and Cst (p < 0.002). SBT following TCO was associated with significant increases in MValv (p < 0.03) and RSBI (p < 0.002). These preliminary findings suggest the importance of proper recumbent body positioning during evidence-based, protocol-guided multimodal chest physiotherapy for ventilator-dependent patients with low CSCI.Key words: alveolar minute volume, body positioning, bronchodilation, carbon dioxide elimination, cardiac output, cervical spinal cord injury, chest optimization, chest physiotherapy, evidence-based, lung hyperinflation, multimodal, noninvasive cardiac output monitoring, rapid shallow breathing index, rehabilitation, spontaneous breathing trial, sputum mobilization, static chest compliance, supine, tetraplegia, Trendelenburg.Abbreviations: ASIA = American Spinal Injury Association, C = cervical, CO = cardiac output, CO 2 = carbon dioxide, CPAP = continuous positive airway pressure, CSCI = cervical spinal cord injury, CSCM = Consortium for Spinal Cord Medicine, Cst = static chest compliance, FIO 2 = fractional inspired oxygen concentration, FRC = functional residual capacity, GIN = gas injection nebulizer, H 2 O = dihydrogen monoxide (water), HR = heart rate, IBW = ideal body weight, IRB = institutional review board, MIE = mechanical insufflator/exsufflator, MValv = alveolar minute volume, NICO = noninvasive CO, RSBI = rapid shallow breathing index, SBT = spontaneous breathing trial, SCI = spinal cord injury, SCO = supine chest optimization, SpO 2 = pulse oximetric saturation, SVN = small volume nebulizer, TCO = Trendelenburg chest optimization, VA = Department of Veterans Affairs, VC = vital capacity, VCO 2 = CO 2 elimination, WBC = white blood cell.