Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.