Azacitidine and venetoclax (Aza-Ven) are part of a new standard of care for elderly patients with Acute Myeloid Leukemia (AML) [In line with recommendations, patients with AML at our centre were routinely admitted during initiation of Aza-Ven for close monitoring for tumour lysis syndrome (TLS). However, hospitalization impacts patient experience and is a significant resource burden. The objectives of this study were to evaluate the incidence of TLS in this population and identify patients who could safely initiate therapy in our outpatient facility. Of the 48 patients who commenced Aza-Ven as inpatients, the incidence of TLS was 25% using Cairo-Bishop (CB) diagnostic criteria but was mostly due to transient increases in uric acid, phosphate or potassium that remained within the normal laboratory reference range. Using Howard diagnostic criteria, TLS incidence was only 2%. Patients who developed CB TLS had a significantly higher baseline white blood count (WBC; = 0.01). Patients with WBC of less than 30 × 10/L subsequently completed outpatient initiation of Aza-Ven ( = 15). Only one of these patients developed mild, transient TLS by CB criteria but not by Howard criteria. Our results demonstrate that a significant portion of patients could safely initiate Aza-Ven in our outpatient facility and avoid unnecessary hospitalization.