• Background Tracheal gas insufflation reduces inspired tidal volume and minute ventilation in spontaneously breathing patients and may facilitate weaning from mechanical ventilation. • Objective To determine if tracheal gas insufflation can reduce ventilatory demand during weaning trials in patients who require prolonged mechanical ventilation. • Methods A reduction in ventilatory demand was defined as a relative decrease in tidal volume, minute ventilation, and mean inspiratory flow during trials with tracheal gas insufflation compared with the values during trials without this therapy. A total of 14 subjects underwent T-piece trials with and without insufflation (flow rate 6 L/min) on 2 consecutive days; the order of insufflation was randomized. Tidal volume, minute ventilation, and mean inspiratory flow were measured at baseline (without insufflation) and 2 hours later. • Results Differences in ventilatory demand were not significant when comparisons were made for condition (tracheal gas insufflation vs no flow) or time (baseline vs 2 hours) for the total group (P = .48). Subjects were classified post hoc as responders (n = 9) or nonresponders (n = 5). Comparisons between responders and nonresponders indicated a significant (P = .02) 3-way multivariate interaction for group (responder vs nonresponder), condition (tracheal gas insufflation vs no flow), and time (baseline vs 2 hours) for ventilatory demand variables. • Conclusion Tracheal gas insufflation can reduce ventilatory demand during weaning trials in some patients who require mechanical ventilation.