Background: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. Identification of determinants of in-hospital mortality and severe left ventricular systolic dysfunction is essential for risk stratification and improving outcomes, particularly in tertiary care settings. Objective To evaluate the clinical profile and identify determinants of in-hospital mortality and severe left ventricular systolic dysfunction (EF <35%) among patients with CAD. Methods This retrospective observational study included 161 adult patients admitted with confirmed CAD to a tertiary care centre in Kerala between January 2012 and December 2016. Demographic characteristics, comorbidities, renal function, and echocardiographic parameters were extracted from medical records. Severe left ventricular systolic dysfunction was defined as ejection fraction (EF) <35%. Associations between baseline variables and in-hospital mortality as well as EF status were analyzed using the Chi-square test. A p-value <0.05 was considered statistically significant. Results Among 161 patients, 78.3% were male, and 59% were aged above 65 years. Diabetes mellitus (67.7%) and hypertension (59.6%) were highly prevalent. Severe left ventricular systolic dysfunction (EF <35%) was observed in 65.2% of patients. The overall in-hospital mortality rate was 19.9%. Chronic obstructive pulmonary disease (COPD) (χ² = 8.91, p = 0.003) and smoking (χ² = 5.21, p = 0.022) were significantly associated with in-hospital mortality. Age, gender, diabetes, hypertension, renal function, and EF category were not significantly associated with mortality. Age category showed a significant association with reduced EF (χ² = 14.27, p = 0.003), with the highest prevalence observed in patients aged 50–65 years. Conclusion In this cohort of CAD patients, severe left ventricular systolic dysfunction was highly prevalent and in-hospital mortality was substantial. COPD and smoking emerged as significant determinants of mortality, while traditional cardiometabolic risk factors were not independently associated with short-term outcomes. Comprehensive management addressing pulmonary comorbidities and modifiable risk factors may improve in-hospital survival among CAD patients.