Background: Studies evaluating VEN with hypomethylating agents in AML patients have reported no incidence of clinical TLS. However, little is known about TLS development in a real-world setting. Here, we investigate our institutional incidence of clinical TLS and describe these patients’ presentations. Methods: This is a single-center, retrospective study of 156 adult pts treated with AZA/VEN for AML between 2015-2019. The primary outcome is the absolute incidence of clinical TLS after AZA/VEN administration per Cairo-Bishop (CB) criteria. Secondary outcomes include median time to TLS, CTCAE grade of TLS, and mortality. All patients received TLS mitigation strategies including fluids, uric acid lowering agents, and frequent lab monitoring. VEN was escalated over 3-4 days, starting at 100 mg, and given with AZA at the standard dose and schedule. Results: The median age was 70 years (22-89); 80 pts (51%) were female. 121 pts (78%) were treatment-naïve, 26 pts (17%) were relapsed, and 9 pts (6%) were refractory. Four pts (3%) developed clinical TLS per CB criteria after AZA/VEN administration. Two pts were relapsed, one pt was treatment-naïve, and one pt had mixed phenotype acute leukemia, B/myeloid. All four pts developed renal insufficiency. No seizures, cardiac arrhythmias, or mortality occurred secondary to TLS. Two pts required renal replacement therapy, and two pts required escalation of care to ICU for TLS management. Median time to TLS onset was 12 hours (10-25) after receiving the first dose of VEN. CTCAE grade 3 TLS occurred in 2 pts (1%) and grade 4 TLS occurred in 2 pts (1%). VEN was held in 2 pts (8, 10 days); no pts required permanent discontinuation of VEN. Baseline features for each patient are listed in the table. Conclusions: Though we report higher rates of clinical TLS compared to prior studies, the incidence of clinical TLS with AZA/VEN remains low. These results support close monitoring of pts, particularly in the first 24 hours of receiving VEN.