Summary Introduction Children with chronic respiratory failure and upper airway disorders may require tracheostomy placement and long-term mechanical ventilation, yet many improve to permit ventilator weaning and decannulation. Methods As a quality improvement project, we conducted a chart review of patients followed by our Ventilator Care Program who underwent evaluation for weaning nocturnal ventilation (NV) and/or decannulation from 2007–2014. We collected patient demographics and characterized location, monitoring techniques, and outcomes for patients undergoing weaning NV or decannulation. We attempted to implement end tidal carbon dioxide (ETCO2) monitoring and used linear regression to compare ETCO2 with morning pCO2. Results Weaning NV was successful in 20/21 patients. Decannulation was successful in 18/21 attempts. Once implemented, ETCO2 was piloted and successfully performed in 12 attempts (29%). Blood testing was performed in 24/42 trials (57%). When measured, the final ETCO2 result partially correlated with morning pCO2 (R2 = 0.53, P < 0.02). Neither blood testing nor ETCO2 was performed for the four patients with unsuccessful attempts. Conclusions Inpatient observation for weaning NV and decannulation is safe and, in most cases, successful. With close observation, weaning NV at home may also be safe. Blood testing and ETCO2 monitoring were frequently utilized, but rarely affected decision-making since signs of respiratory distress were observed clinically prior to testing. ETCO2 monitoring may provide reassurance without venipuncture. With our experience, we propose an algorithm for weaning NV and decannulation.