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Background: Acute coronary syndrome (ACS) refers to a spectrum of conditions compatible with acute myocardial ischemia and/or infarction that are usually due to an abrupt reduction in coronary blood flow. Objective: The objective of the study was to assess the treatment outcome and associated factors for ACS. Methods: A retrospective cross-sectional study was conducted from January 1, 2012 to December 31, 2014. Results: Of 124 ACS patients who were admitted during the 3 years’ period, 90 (72.6%) were diagnosed with ST segment elevation myocardial infarction (STEMI). The mean age was 56.3 ± 13.7 years. The average length of hospital stay was 9.77 ± 6.42 days. The average time from onset of ACS symptoms to presentation in the emergency department was 3.8 days (91.7 hours). In about 76 (61.3%) patients, hypertension was the leading risk factor for development of ACS, and 36.4% of ACS patients were either Killip class III or IV. Biomarkers were measured for 118 (95.2%) patients, and 79.2% of patients had ejection fraction of less than 40% and 29.2% had less than 30%. In-hospital medication use includes loading dose of aspirin (79%), anticoagulants (77.4%), beta blockers (88.1%), statins (85.5%), morphine (12.9%), and nitrates (35.5%). The in-hospital mortality was 27.4%. The predictors for in-hospital mortality were age ( P  = .042), time from symptom onset to presentation ( P  = .001), previous history of hypertension ( P  = .025), being Killip class III and IV ( P  = .001), and STEMI diagnosis ( P  = .005). Conclusions: The medical management of ACS patients in Tikur Anbessa Specialized Hospital (TASH) was in line with the recommendations of international guidelines but in-hospital mortality was extremely high (27.4%).