Background: Patients with chronic obstructive pulmonary disease (COPD) exacerbation can develop acute coronary syndrome (ACS). The cardiovascular mortality and morbidity in COPD exacerbation is often under diagnosed. Objectives: Our study assessed the incidence of ACS in patients with COPD exacerbation, the risk factors associated with it and 28 day all-cause mortality of patients with COPD exacerbation. Methods: A prospective observational study was conducted on consecutive patients admitted with COPD exacerbation from February 2016 to August 2017. They were monitored during the hospital stay for occurrence of ACS and followed up till 28 days. Results: 298 patients were evaluated. Incidence of ACS was 7.71%. ACS was commoner in patients with severe COPD (65.21% Vs 34.78%), diabetes mellitus (18.98% Vs 3.6%, p= 0.001) and systemic hypertension (12.5% Vs 5.44%, p= 0.03). Patients with ACS had a higher mean age (69.65 Vs 62.98yrs, p=0.0001) and mean number of previous exacerbations (1.82 Vs 1.60, p=0.032) but lower mean forced expiratory volume in 1st second (32.3ml Vs 56.25ml, p=0.001).Hypoxic patients were at higher risk for developing ACS (14.71% Vs 5.65%, p=0.013). The 28-day all-cause mortality was 15.77% and was higher among patients with severe COPD compared with mild COPD (4.36% Vs 3.35%)and those with ACS compared with no ACS (34.78% Vs 14.18%, p= 0.02). Conclusion: Incidence of ACS in COPD exacerbation was high. More care needs to be exercised to identify cardiac events and thus reduce the mortality and morbidity of COPD patients.