Objective: To analyze comorbidities and outcomes in patients with tardive dyskinesia (TD) during psychiatric inpatient management. Methods: We conducted a case-control study using the Nationwide Inpatient Sample. It included 77,022 adult inpatient admissions for mood disorders and schizophrenia. Cases had a secondary diagnosis of TD, and controls without TD were matched for age. Multivariable logistic regression was used to generate odds ratio (OR). Results: Majority of TD patients were older age adults (50–64 years; 40%), and were in nearly equal proportions of men and women. African Americans had two-fold higher odds of TD. TD patients had a higher likelihood for cardio-metabolic comorbidities-obesity (OR 1.61, 95% CI 1.481–1.756), hypertension (OR 1.78, 95% CI 1.635–1.930) and diabetes (OR 1.54, 95% CI 1.414–1.680) compared to controls. They also had 1.5-fold increased risk of comorbid drug abuse. Patients with schizophrenia and bipolar disorder (depressive) had four-fold higher odds of TD. TD patients had about six-fold higher odds of severe morbidity. They had a higher likelihood of extended hospitalization stay by 6.36 days (95% CI 6.174–6.550) and higher cost by $20,415 (95% CI 19537–21293) compared to controls. Conclusion: Psychiatric inpatients with TD have greater severity of illness, and those with schizophrenia and bipolar disorders are at highest risk. Presence of TD portends poor hospital outcomes and need for higher acute inpatient care.