INTRODUCTION: Immune checkpoint-inhibitor (ICI) induced colitis is increasingly being recognized as a serious adverse event of ICIs. However, there are limited epidemiological studies with small sample sizes. We sought to use a large database to better evaluate the epidemiology of ICI-induced colitis and describe underlying associations. METHODS: A commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 US healthcare systems was surveyed. A cohort of patients who were on ICIs (nivolumab, pembrolizumab, ipilimumab, avelumab, durvalumab, and atezolizumab) between 2015 and 2020 was identified. Subsequently, patients who developed new Systematized Nomenclature of Medicine-Clinical Terms diagnosis of colitis after taking ICIs were selected. The prevalence of ICI-induced colitis was calculated and underlying associations were described. RESULTS: Of the 35,547,340 patients in the database, we identified 14,850 (0.04%) with history of ICI use. There were 470 (3.2%) patients who developed a new diagnosis of ICI-induced colitis after at least 1 day of starting ICI therapy. Patients who developed ICI-induced colitis were more likely to be Caucasian [OR: 1.44; 95% CI 1.07–1.93] and younger than 65 years [OR: 1.22; 95% CI 1.01–1.46]. There were no statistically significant gender-based differences. When compared to patients on ICI therapy who did not develop colitis, patients with ICI-induced colitis were more likely to be obese [OR: 1.47; 95% CI 1.19–1.80] with a history of alcohol use [OR: 1.48; 95% CI 1.23–1.79]. Patients who received Nivolumab [OR: 1.32; 95% CI 1.09–1.58] and Ipilimumab [OR: 3.58; 95% CI 2.91–4.39] had the highest odds of developing ICI-induced colitis (Figure 1). The majority of cases were diagnosed in the first 6 months of therapy. Proportion of ICI-induced colitis over a 5-year interval is presented in Figure 2. CONCLUSION: This is the largest study evaluating the epidemiology of ICI-induced colitis. Patients with ICI-induced colitis were more likely to be Caucasian, younger than 65, with history of obesity and alcohol use. Special consideration should be given prior to initiating Nivolumab and Ipilimumab and close follow-up of gastrointestinal symptoms is warranted especially in the first 6 months. The risk of ICI-induced colitis should be discussed with all patients prior to initiating these agents.Figure 1.: Odds ratio of selected immune checkpoint-inhibitors demonstrating the risk of immune checkpoint-inhibitor induced colitis. *Only Nivolumab and Ipilimumab were statistically significant.Figure 2.: Proportion of Immune checkpoint-inhibitors over a period of 5 years.