Purpose: Spica casting and elastic stable intramedullary nailing (ESIN) are treatment options for femur fractures in preschool-age children. Clinical practice guidelines (CPG) on the subject are only of moderate or limited strength, which may lead to variation in practice. The purpose of this study is to compare the rate of reoperation in young children undergoing these procedures in a large, nationally representative population. Methods: The Pediatric Health Information System, a national database consisting of 49 children’s hospitals, was queried for patients between 3 and 6 years of age undergoing spica casting or ESIN for a diaphyseal femur fracture between 2010 and 2017. Non-diaphyseal fractures, subjects with associated syndromes or neuromuscular disorders, and pathologic fractures were excluded. Demographic information was collected for each subject as well as data regarding subsequent reoperations, readmissions, and returns to the emergency department. Elective ESIN removal was not considered an unplanned reoperation. Univariate analysis was followed by purposeful entry multivariate regression to adjust for confounding factors. Results: Analysis included 4059 subjects with a mean age of 3.9±1.1 years, of which 3011 (74%) were male. The median length of hospitalization was 1 day for spica casts (range 1-32) and 2 days for ESIN (range 1-167, p<0.01). Unplanned reoperation was performed in 227/2878 (8%) of children with a spica cast and 35/1181 (3%) of those with ESIN (p<0.01). The most common secondary procedures performed were repeat closed reduction (60%) and ESIN (26%). After controlling for age and other factors in a multivariate model, spica casting resulted in 4.4 times higher odds of unplanned reoperation than ESIN (95% CI 2.9-6.7, p<0.01). Multivariate sub-analysis of the spica cast cohort revealed that each year of increasing age resulted in 1.3 times higher odds of reoperation (95% CI 1.1-1.6, p<0.01). Furthermore, children that were aged 5 or 6 years at the time of spica casting had 1.9 times higher odds of requiring a subsequent procedure compared to 3 and 4 year-olds (95% CI 1.3-2.7, p<0.01). Conclusion: In this large, nationally representative cohort, spica casting resulted in 4.4 times higher odds of requiring an unplanned reoperation than ESIN. Spica casting in older children, specifically 5 years and above, yielded higher odds of reoperation.