Background: During spontaneous breathing trial, low-pressure support is thought to compensate for endotracheal tube resistance, but it actually should provide overassistance. Automatic tube compensation is an option available in the ventilator to compensate for flow-resistance of endotracheal tube. Its effects on patient effort have been poorly investigated. We aimed to compare the effects of low-pressure support and automatic tube compensation during spontaneous breathing trial on breathing power and lung ventilation distribution. Results: We performed a randomized crossover study in 20 patients ready to wean. Each patient received both methods for 30 min separated by baseline ventilation: pressure support 0 cmH2O and automatic tube compensation 100% in one period and pressure support 7 cmH2O without automatic tube compensation in the other period, a 4 cmH2O positive end-expiratory pressure being applied in each. Same ventilator brand (Evita XL, Draeger, Germany) was used. Breathing power was assessed from Campbell diagram with esophageal pressure, airway pressure, flow and volume recorded by a data logger. Lung ventilation distribution was assessed by using electrical impedance tomography (Pulmovista, Draeger, Germany). During the last 2 min of low-pressure support and automatic compensation period breathing power and lung ventilation distribution were measured on each breath. Breathing power generated by the patient’s respiratory muscles was 7.2 (4.4–9.6) and 9.7 (5.7–21.9) J/min in low-pressure support and automatic tube compensation periods, respectively (P = 0.011). Lung ventilation distribution was not different between the two methods. Conclusions: We found that ATC was associated with higher breathing power than low PS during SBT without altering the distribution of lung ventilation.