Mechanically ventilated pediatric intensive care patients usually receive an analgesic and sedative to keep them comfortable and safe. However, common drugs like fentanyl and midazolam have a long context sensitive half time, resulting in prolonged sedation and an unpredictable extubation time. Children often awake slowly and struggle against the respirator, although their respiratory drive and their airway reflexes are not yet sufficient for extubation. In this pilot study, we replaced fentanyl and midazolam at the final phase of the weaning process with remifentanil and propofol. Twenty-three children aged 3 months–10 years were enrolled. Remifentanil and propofol revealed throughout excellent or good weaning conditions with rapid transition from hypnosis to the development of regular spontaneous breathing, airway protective reflexes, and an appropriate level of alertness. Extubation time following discontinuation of the remifentanil and propofol infusion was only 24 ± 20 min (5–80 min). We conclude that the combination of remifentanil and propofol is a promising option to improve the weaning conditions of pediatric intensive care patients. Randomized controlled trials are needed to compare remifentanil and propofol with conventional weaning protocols.