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All-trans-retinoic acid (ATRA) is the standard of care for the management of acute promyelocytic leukemia (APL), but can be associated with differentiation syndrome (DS). Over a seven-year period, we sought to determine the impact of ATRA initiation time on the development of DS. ATRA administration time had no impact on DS occurrence (p = =0.13), APL risk (p = =0.28) or regimen received (p = =0.1). Patients with higher mean body mass index (BMI) were more likely to develop moderate or severe DS (p = =0.02). Early treatment of APL is essential and maybe strongly considered in patients with elevated BMI. Keywords: Acute promyelocytic leukemia (APL), All-trans retinoic acid (ATRA), Differentiation syndrome