Objective: DiGeorge Syndrome (DGS) is a common multisystem disorder associated with deletions on chromosome 22q11.2. Our objective is to evaluate the psychiatric comorbidities and demographics of patients suffering from DGS in a nationally representative dataset on inpatient hospitalizations. Methods: The Nationwide Inpatient Sample for the year 2005−2017 was used for this study. Data on patients with DiGeorge syndrome were collected by using the International Classification of Diseases code. Univariate and multivariate logistic regression analysis was performed. Results: In our study, the average age was 30.4 years (n = 6,563), with 59.9% male, and 61.8% of patients were white. There was a high prevalence of mood disorders (24.7%) and anxiety disorders (16.4%), followed by schizophrenia and other psychotic condition (14.0%). In patients with mood disorders, 8% had Major Depressive Disorder, and 7% had bipolar depression. Overall composite of psychiatric comorbidities was present in 2,959 (45.1%) of patients. The mean length of stay was 6.58 days, and 77% of patients had routine discharge to home. In the adjusted analysis, the average length of stay was 8.6 days vs. 6.7 days (p ＜ 0.001) in patients with and without psychiatry comorbidities. In comparison to routine discharge, patients with psychiatry comorbidities were more likely to be discharged to other healthcare facilities (odds ratio [OR]: 1.28, p ＜ 0.001) and discharged against medical advice (OR: 3.45, p ＜ 0.001). Conclusion: Patients with DGS have worse outcomes with a higher rate of discharge to other healthcare facilities and a higher rate of being discharged against medical advice. Further large scale randomize studies are indicated.