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Background Tumor lysis syndrome (TLS) is a life‐threatening oncologic emergency associated with fatal complications including arrhythmia. The epidemiology and mortality outcomes of arrhythmia in TLS are scarcely studied in the literature. Methods We used the National Inpatient Sample (NIS) to study the prevalence and outcome of arrhythmia in patients hospitalized with TLS (ICD‐9 code 277.88) from 2009 to 2014. Baseline characteristics, burden of arrhythmia, and pertinent outcomes were analyzed. Multivariable regression analysis was performed to identify the impact of underlying malignancy in predicting TLS‐related mortality. Results A total of 9034 cases of arrhythmia among 37 861 TLS patients were identified. More than half of the arrhythmia cases (67%) were found among white old (>65) males admitted to large bed size and urban teaching hospitals. Arrhythmic cohort showed higher frequency of comorbidities such as fluid‐electrolyte disturbances, hypertension, congestive heart failure, renal failure, dyslipidemia, diabetes, pulmonary circulatory disorders, chronic pulmonary disease, coagulopathy, and deficiency anemia. The most common malignancies were leukemia, lymphoma, metastatic tumor, and solid tumor without metastasis. We found significantly higher odds of in‐hospital mortality among patients with TLS compared to general inpatient population on unadjusted (OR 9.69, 95% CI: 9.27‐10.13, P, A total of 23.9% of (n = 9034) encounters with arrhythmia were identified, out of 37 861 TLS‐related hospitalizations. The trends in the prevalence of arrhythmia were stable with rates ranging from 19.8% to 25.8%, with the highest frequency recorded in 2014 (25.8%) (Figure 1A). Atrial fibrillation (13.6%) was the most common arrhythmia followed by ventricular tachycardia in 2.6% of patients (Figure 1B).