Background::Conventional pressure support ventilation (PSn P) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PSn N) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PSn N and PSn P in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.n Methods::Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.Results::Total AI of PSn N was consistently lower than that of PSn P in COPD (3% n vs. 93%, n P = 0.012 for 100% support level; 8% n vs. 104%, n P = 0.012 for 150% support level), ARDS (8% n vs. 29%, n P = 0.012 for 100% support level; 16% n vs. 41%, n P = 0.017 for 150% support level), and post-operative patients (21% n vs. 35%, n P = 0.012 for 100% support level; 15% n vs. 50%, n P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PSn P but not during PSn N in patients with COPD or ARDS. Patients’ inspiratory efforts for triggering and total inspiration were significantly lower during PSn N than during PSn P in patients with COPD or ARDS under both support levels (n P < 0.05). There was no difference in breathing patterns between PS n N and PSn P.n Conclusions::PSn N improves patient-ventilator synchrony and generates a respiratory pattern similar to PSn P independently of any level of support in patients with different respiratory system mechanical properties. PSn N, which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PSn P.n Trial Registration::ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.“,”Background::Conventional pressure support ventilation (PSn P) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PSn N) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PSn N and PSn P in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.n Methods::Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.Results::Total AI of PSn N was consistently lower than that of PSn P in COPD (3% n vs. 93%, n P = 0.012 for 100% support level; 8% n vs. 104%, n P = 0.012 for 150% support level), ARDS (8% n vs. 29%, n P = 0.012 for 100% support level; 16% n vs. 41%, n P = 0.017 for 150% support level), and post-operative patients (21% n vs. 35%, n P = 0.012 for 100% support level; 15% n vs. 50%, n P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PSn P but not during PSn N in patients with COPD or ARDS. Patients’ inspiratory efforts for triggering and total inspiration were significantly lower during PSn N than during PSn P in patients with COPD or ARDS under both support levels (n P < 0.05). There was no difference in breathing patterns between PS n N and PSn P.n Conclusions::PSn N improves patient-ventilator synchrony and generates a respiratory pattern similar to PSn P independently of any level of support in patients with different respiratory system mechanical properties. PSn N, which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PSn P.n Trial Registration::ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.