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To quantify the daily risk of unplanned extubation (UE) in newborns based on developmental and anatomical factors.Prospective cohort of ventilated newborns over an 18-month period in a level IV neonatal intensive care unit (NICU). We captured UEs through four data streams. We generated multivariable logistic regression models to assess the association of UE with chronological age, birth weight, and postmenstrual age.During the study, 718 infants were ventilated for 5,611 patient days with 117 UEs in 81 infants. The daily risk of UE had a significant, nonlinear relationship (p < 0.01) with chronological age, decreasing until day 7 (odds ratio [OR]: 0.5; 95% confidence interval [CI]: 0.17-1.47) and increasing after day 7 (day 7-28, OR: 1.36, 95% CI: 1.06-1.75; and >28 days, OR: 1.06, 95% CI: 1.0-1.14). Birth weight and postmenstrual age were not associated with UE. Adverse events occurred in 83/117 (71%) UE events. Iatrogenic causes of UE were more common in younger, smaller infants, whereas older, larger infants were more likely to self-extubate.The daily risk and causes of UE change over the course of an infant's NICU hospitalization. These data can be used to identify infants at the highest risk of UE for whom targeted proactive interventions can be developed.