Abstract BACKGROUND Inflammatory Bowel Disease (IBD) is a proinflammatory condition that is known to be associated with depression. Research examining causality suggests that Crohn's disease (CD) or ulcerative colitis (UC) patients are vulnerable to triggering pre-existing mental health conditions and that conversely, a pre-existing disorder such as depression may have an effect on the disease process and course of IBD. There is a paucity of comprehensive studies examining the downstream effects of depression on patients with IBD such as readmission rates and mortality. The complexity of the interaction between depression and IBD remains a fertile ground for further investigations in terms of pathological reciprocity and downstream consequences. METHODS In this retrospective observational study, patients were queried from the National Readmissions Database from 2016 to 2019. ICD-10 codes were used to identify patients with Crohn’s disease, ulcerative colitis, and depression. Primary outcomes were mortality and readmission rates at 30 days and 90 days. Secondary outcomes were index admission mortality, hospital length of stay (LOS), and total hospitalization charges (TOTHC) at 30 and 90 days respectively. The top 10 readmission diagnoses in each subgroup were also identified. RESULTS For patients with CD and depression, the mean age at readmission was 51.6 years with a high readmission and mortality rate at 30 days (readmission rate 5.2%, p<0.01; mortality rate 2.8%, p<0.01) which increased significantly at 90 days (readmission rate 8.4%, p<0.01). Hospital LOS and TOTHC remained relatively the same compared to the index admission for both 30-day and 90-day readmissions (Table 1,2). A similar trend was seen for UC and depression as well: mean age at readmission was 51.4 years with a high readmission rate and mortality at 30 days (readmission rate 5.0%, p<0.01; mortality rate 2.6%, p<0.01) which increased significantly at 90 days (readmission rate 8.4%, p<0.01; mortality rate 2.9%, p<0.01). Sepsis, hypertensive heart disease accompanied by heart failure and/or chronic kidney disease, acute kidney injury, hypoxia, and acute depressive episodes were the top primary associated readmission etiologies at 30 days and 90 days when correlated with a diagnosis of UC or CD. (Table 1, 2). CONCLUSION Our investigation revealed that patients affected by both depression and either UC or Crohn’s disease exhibited elevated readmission rates and a notably amplified mortality risk at 30 days post-readmission, with a more substantial increase observed at the 90-day mark. These findings underscore the significance of healthcare providers routinely screening for depression, addressing the management of mental health, and acknowledging the considerable impact it has on patients with co-occurring chronic diseases like UC or CD as an integral facet of comprehensive care. Table 1 Table 2