Background: The risk of developing Tumor Lysis Syndrome (TLS) is widely understood in highly proliferative cancers. Clinicians have adopted the “Howard Criteria” in evaluating clinical characteristics that lead to a higher propensity to develop TLS following chemotherapy  . However, no real-world data has been published that quantifies TLS risk factors by cancer type. Methods: The Integra database of 17 community oncology accounts was queried for patients ≥18 years of age having a TLS ICD10 code between 1/1/2017 and 9/30/2020. Patients were excluded if they had a TLS diagnosis without anti-cancer treatment data. To remove bias we excluded patients who received rasburicase on a preventative basis. Among patients with a TLS diagnosis, clinical lab values were collected prior to the dates of TLS diagnosis and anti-neoplastic therapy. A multivariate risk regression analysis was performed to evaluate TLS risk by disease site, by baseline characteristics, and lab values. The risk analysis compared TLS patients diagnosed with CLL, DLBCL, CML, LGBCL, TCL, MM, and MCL to patients in the database with those cancers that did not develop TLS. Results: Relative risk of developing TLS in the selected tumor types was estimated with reference to DLBCL. Both TCL and MCL had higher relative risk ratios at 1.43 and 1.38, respectively (Fig 1). In CLL, venetoclax treatment was highly correlated with increased TLS risk (Fig 2). Multivariate regression analysis indicated that factors associated with developing TLS differed by each tumor type. In CLL low potassium and abnormal WBC are most closely associated with TLS (Fig 3). DLBCL regression analysis found that elevated WBC were elevated PO4 levels were highly correlated with TLS (Fig 3). Elevated WBC and Ca++ increased risk of TLS in LGBCL (Fig 3). MM had several risk factors highly correlated with developing TLS including abnormal WBC, abnormal LDH, elevated PO4, and low Ca++ (Fig 3). Conclusions: There are numerous risk factors unique to each cancer type with a measurable impact on TLS risk that can be identified and mitigated through preventative management. This study is limited to the EMR and administrative claims data of those individuals who are being treated in a community oncology setting. Residual confounding and bias may exist due to entry error and unobserved patient characteristics.