e20011 Background: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small cell lung cancer (NSCLC). Limited data exists for a comprehensive cardiotoxicity profile analysis for osimertinib in NSCLC patients. Methods: Data was retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System between 7/2016 and 1/2024. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated. Corrected QT interval was calculated using the Fredericia formula. QT prolongation was defined as a QTc >500 milliseconds (ms). Results: A total of 116 participants with NSCLC on osimertinib were included in the analysis with median age of 52.2 years, 69.8% female, and mean 1.52 years of follow-up. The study population was 93.1% of white race, and significant comorbidities within the overall population included hypertension (70.7%), hyperlipidemia (53.4%), tobacco use (38.8%), coronary artery disease (18.1%) and diabetes mellitus (15.5%) (Table). Out of 85 patients with no specified prior cardiac abnormalities, 29.4% developed new onset cardiac abnormalities (Table). The median QTc increased from 429 ms to 444 ms after starting osimertinib, and 8.8% of patients had QTc >500 ms. Conclusions: Osimertinib is used in NSCLC and appears to be associated with an increase in cardiac abnormalities. A direct causal relationship between osimertinib use and cardiotoxicity has not yet been established. Given the strong association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram and echocardiographic abnormalities. [Table: see text]