ABSTRACT: Background: There is limited knowledge about the effect of position change on regional lung ventilation in patients with respiratory failure. This study aimed to examine the physiological alteration of regional lung ventilation during the position change from lying in bed to sitting on a wheelchair. Methods: In this study, 41 patients with respiratory failure who were weaned from the ventilators were prospectively enrolled. The electrical impedance tomography (EIT) was used to assess the regional lung ventilation distribution at four time points (Tbase: baseline, supine position in the bed, T30min: sitting position in the wheelchair after 30 min, T60min: sitting position in the wheelchair after 60 min, Treturn: the same supine position in the bed after position changing). The EIT-based global inhomogeneity (GI) and center of ventilation (CoV) indices were calculated. The EIT images were equally divided into four ventral-to-dorsal horizontal regions of interest (ROIs 1-4). Depending on the improvement in ventilation distribution in the dependent regions at T60min (threshold set to 15%), the patients were divided into the dorsal ventilation improved (DVI) and not improved (non-DVI) groups. Results: When the patients moved from the bed to a wheelchair, there was a significant and continuous increase in ventilation in the dorsal regions (ROI 3 + 4: 45.9 ± 12.1, 48.7 ± 11.6, 49.9 ± 12.6, 48.8 ± 10.6 for Tbase, T30min, T60min, and Treturn, respectively; p = 0.015) and CoV (48.2 ± 10.1, 50.1 ± 9.2, 50.5 ± 9.6, and 49.5 ± 8.6, p = 0.047). In addition, there was a significant decrease in GI at T60min compared with Tbase. The DVI group (n = 18) had significantly higher oxygenation levels than the non-DVI group (n = 23) after position changing. ROI4Tbase was significantly negatively correlated with the ΔSpO2 (R = 0.72, p < 0.001). Using a cutoff value of 6.5%, ROI4Tbase had 79.2% specificity and 58.8% sensitivity in indicating the increase in the dorsal region related to the position change. The corresponding area under the curve (AUC) was 0.806 (95% CI, 0.677-0.936). Conclusions: Position change may improve the ventilation distribution in the study patients. The EIT can visualize real-time changes of the regional lung ventilation at the bedside to guide the body position change of the patients in the intensive care unit (ICU) and measure the effect of clinical practice. Trial Registration: Effect of Early Mobilization on Regional Lung Ventilation Assessed by EIT, NCT04081129. Registered 9 June 2019-Retrospectively registered. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S00096WT&selectaction=Edit&uid=U00020D9&ts=2&cx=v2cwij.