Background: Tumor lysis syndrome (TLS) is a well-recognized complication in cancer patients with high tumor burden receiving chemotherapy and is associated with increased morbidity and mortality. Our study specifically looks at longitudinal trends in outcomes and healthcare utilization in TLS patients over time. Methods: Adult patients with TLS admitted between 2012-2017 were identified from the Nationwide Inpatient Sample database. Statistical tests for trends of outcomes (including mortality and Acute Kidney Injury (AKI)) and resource utilization across six years were performed. Multivariable logistic regression was used to evaluate risk factors for mortality in TLS. Results: A total of 57,760 patients met inclusion criteria, with 15.2% having Solid Tumors (ST) and rest hematological cancers (HC). Patients with ST were predominantly older (mean age 60.7 vs 56.4 years, p < 0.0001) and female (44.6% vs 35.2%, p < 0.0001). ST patients had higher mortality (32.3% vs 19.1, p < 0.0001) and AKI (68.6% vs 59.3%, p < 0.0001); but shorter hospitals stay (10.5 vs 15.8 days, p < 0.0001) and lower hospital charges ($34k vs $59k, p < 0.0001). Multivariable analysis showed increased inpatient mortality with ST compared to HC (OR 1.54, 95% CI 1.35-1.76, p < 0.001). Although mortality in ST non-significantly decreased from 36.2% to 28.9% over time, it remained constant in HC. Rate of AKI increased significantly in both cohorts. There were no significant temporal changes in hospital charges in either group, although those with HC were noted to have a decrease in length of stay, from 16.8 to 15.6 days (p = 0.02) over time. Trends of outcomes and resource utilization in TLS. Conclusions: TLS in ST has worse prognosis than HC, although mortality has improved over years. However, inpatient mortality remains largely unchanged in HC. Despite therapeutic advances,