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Purpose: To compare neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), adaptive support ventilation (ASV) and Smartcare pressure support (Smartcare/PS) with standard pressure support ventilation (PSV) regarding their effectiveness for weaning critically ill adults from invasive mechanical ventilation (IMV). Methods: Electronic databases were searched to identify parallel-group randomized controlled trials (RCTs) comparing NAVA, PAV, ASV, or Smartcare/PS with PSV, in adult patients under IMV through July 28, 2021. Primary outcome was weaning success. Secondary outcomes included weaning time, total MV duration, reintubation or use of non-invasive MV (NIMV) within 48 h after extubation, in-hospital and intensive care unit (ICU) mortality, in-hospital and ICU length of stay (LOS) (PROSPERO registration No:CRD42021270299). Results: Twenty RCTs were finally included. Compared to PSV, NAVA was associated with significantly lower risk for in-hospital and ICU death and lower requirements for post-extubation NIMV. Moreover, PAV showed significant advantage over PSV in terms of weaning rates, MV duration and ICU LOS. No significant differences were found between ASV or Smart care/PS and PSV. Conclusions: Moderate certainty evidence suggest that PAV increases weaning success rates, shortens MV duration and ICU LOS compared to PSV. It is also noteworthy that NAVA seems to improve in-hospital and ICU survival. (c) 2021 Elsevier Inc. All rights reserved.