Background: We sought to evaluate the relationship between determinants of intestinal failure (IF) and achieving enteral autonomy from parenteral nutrition (PN) in a large single-center cohort of children. Methods: This is a retrospective chart review of pediatric subjects enrolled in a database for the Center for Advanced Intestinal Rehabilitation at Children's of Alabama from 1989 to 2016. IF was defined as dependence on PN for >60 days. Subjects were included if they were followed since birth or infancy for a minimum of 3 months and sufficient documentation of study variables were available. Gestational age, race, diagnosis, anatomy (percent small and large bowel remaining, presence of ileocecal valve [ICV]), county of residence (rural/urban), and days of PN use were recorded. Kaplan-Meier curves and parametric survival regression models were used to investigate the relationship between the demographic and clinical variables with the length of PN use. Results: Initially, 290 subjects were available to review. After inclusion/exclusion were applied, 158 subjects remained. Gestational age, diagnosis (necrotizing enterocolitis), small-bowel length (>50%), and presence of an ICV were all positive predictors for reaching enteral autonomy. Residual colon length was associated with shorter duration of PN in days. Conclusion: Enteral autonomy is a key outcome among children with IF. In our cohort, we found that gestational age, diagnosis, remaining small bowel, and presence of ICV are positive predictors for reaching this important milestone. Colon length is also an important factor with respect to duration of PN in days.