Objective: Our aim was to determine if co-diagnosis of major depressive disorder (MDD) influenced inpatient outcomes of hypertensive emergency (HTNE) admissions. Methods: We analyzed the national inpatient sample (2012-2019) for HTNE admissions of ages >18 years. The primary outcomes were hospital length of stay (LOS), costs (adjusted for inflation), adverse hospital events (need for mechanical circulatory support and intubation) and in-hospital mortality. Secondary outcomes included predictors of mortality in HTNE patients with MDD. Demographic (age, sex, race) and clinical (history of hypertension, hyperlipidemia, stroke, chronic kidney disease, myocardial infarction, obesity, smoking) factors were adjusted for. Data was analyzed in STATA 16.0, and adjusted odds ratios (AOR) were calculated using linear and logistic regression method. Results: Our study included 149,366 weighted discharges for HTNE. Prevalence of MDD was 9.6% (n=14,339). Average age of the patients were 48 years. 65% were Caucasians, 57% were females and average LOS was 5.5 days. Patients with MDD had longer LOS (6.4 vs 5.1 p<0.001). The adjusted hospital cost was $25,923 higher in patients with MDD (p<0.001), and they also had higher odds of inpatient mortality (AOR 1.76, [1.53 -1.83], P < 0.001). The odds for requiring mechanical circulatory support were higher in patients with MDD (AOR 1.44, P < 0.001). African American men had the highest inpatient costs and LOS. Several conditions increased mortality in HTNE patients with MDD including obesity, cerebrovascular disease (CVD) and end-stage renal disease (ESRD). (Figure 1) Conclusion: Major depressive disorder has an important and unexplored association with hypertension. Our study demonstrates that patients admitted with hypertensive emergency have increased hospital LOS, cost, adverse hospital events and mortality when they have concomitant depression.