Background: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the world. Although no countrywide study has been done on cardiovascular disease (CVD) in Ethiopia some hospital based studies have shown the incidence of CVD is progressively increasing. Methodology: A retrospective cross sectional study was conducted on the clinical profile of patients with Acute Coronary Syndrome (ACS) In Tikur Anbessa and AaBET hospitals using a structured questionnaire from January 2016 to February 2018. The data were entered, analyzed and interpreted using SPSS version 20 software. Result: Of 142 patients with ACS, 62 (48.6%) were diagnosed as STEMI. The mean age was 57.5±12.09 years. The average time from onset of ACS symptoms to presentation in the emergency department was 2.4 days (61.96 hours) ±48.85. In about 101 (71.1%) patients, hypertension was identified as a risk factor for development of ACS. Nearly fifteen percent (14.8 %) of ACS patients in Tikur Anbessa and AaBET hospitals were either Killip class III or IV. The in-hospital mortality was 9.8%. Predictors of inhospital mortality in Tikur Anbessa and AaBET hospitals included female sex (P=0.016), time from symptom onset to presentation (P=0.04), being Killip class III and IV (P=0.001), and STEMI diagnosis (P=0.018). Conclusion: Patients with ACS have delayed presentation to the hospital from onset of symptoms. Patients had similar risk profiles with the developed world, but have higher mortality. Being female, delayed presentation, having STEMI, and higher Killip class was found to be independent predictors of in hospital mortality in Tikur Anbessa and AaBET Hospitals.