Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia (AML) that was previously one of the most fatal forms of acute leukemia. With advances in diagnosis and treatment, APL has become one of the most curable myeloid leukemias. The major reason for treatment failure in APL is early death after initiation of treatment. We performed a retrospective cross-sectional analysis of the Healthcare Cost and Utilization Project 2016 and 2019 Kids’ Inpatient Database, with the diagnosis of APL or AML not in remission as defined by ICD-10-CM codes. We compared complications and outcomes associated with APL and AML (exclusive of APL) in hospitalized children in the U.S. and described yearly national incidence. The national incidence of APL was 2.2 cases per million children per year. Children with APL were more likely to have cardiopulmonary complications (OR 1.79; CI 1.20–2.67; p = 0.004), coagulation abnormalities or DIC (OR 7.75; CI 5.81–10.34; p < 0.001), pulmonary hemorrhage (OR 2.18; CI 1.49–3.17; p < 0.001), and intracranial hemorrhage (OR 10.82; CI 5.90–19.85; p < 0.001) and less likely to have infectious complications (OR 0.48; CI 0.34–0.67; p < 0.001) compared to children with AML. In-hospital mortality rates were similar in children with APL and AML (4.2% vs 2.6%; OR 1.62; CI 0.86–3.06; p = 0.13), while the median length of stay for children who died from APL was shorter compared to AML (2 (IQR: 1–7) versus 25 (IQR: 5–66) days; p < 0.05). Hemorrhagic complications occur more often, and infectious complications occur less often in hospitalized children with APL compared to AML.