BACKGROUND: We sought to describe adverse events associated with unplanned extubation (UE) and to explore risk factors for serious adverse events post-UE among infants who experienced UE. METHODS: Data were prospectively collected on all infants who had a UE event at a single institution over a 4-y period. Demographic information and information on outcomes were obtained retrospectively. We described the frequency of post-UE adverse events: success or failure of extubation trial if offered, rate of re-intubation, post-UE changes in ventilator settings, and serious adverse events post-UE (eg, need for cardiopulmonary resuscitation, clinical sepsis, and death or tracheostomy prior to discharge). We used a multivariate logistic regression model to identify the risk factors associated with serious adverse events. RESULTS: There were 134 documented UE events. Agitation was the most common known cause. After UE, 49% of the subjects were given a trial of extubation, and 65% of the trials were successful at 48 h. Cardiopulmonary resuscitation (CPR) was performed in 13% of cases. In subjects requiring immediate re-intubation, mean airway pressure (P aw) and oxygen requirement increased in 33% and 55% of the subjects, respectively. Post-UE clinical sepsis occurred in 17% of subjects. Higher pre-UE P aw and difficult re-intubation were associated with a need for CPR. Subjects who received CPR had increased odds (3.7؋) of developing clinical sepsis. CONCLUSION: UE can result in serious adverse events, including hemodynamic instability and possibly an increased risk for clinical sepsis. Difficult re-intubation was associated with a higher risk of needing CPR and, later, tracheostomy and death.