There is a lack of knowledge about the real incidence of acute coronary syndrome (ACS) in patients with COVID-19, their clinical characteristics, and their prognoses. We investigated the incidence, clinical characteristics, risk factors, and outcomes of ACS in patients with COVID-19 in the emergency department. We retrospectively reviewed all COVID-19 patients diagnosed with ACS in 62 Spanish emergency departments between March and April 2020 (the first wave of COVID-19). We formed 2 control groups: COVID-19 patients without ACS (control A) and non-COVID-19 patients with ACS (control B). Unadjusted comparisons between cases and control subjects were performed regarding 58 characteristics and outcomes. We identified 110 patients with ACS in 74,814 patients with COVID-19 attending the ED (1.48% 95% confidence interval {CI} 1.21-1.78%). This incidence was lower than that observed in non-COVID-19 patients (3.64% 95% CI 3.54-3.74%; odds ratio OR 0.40 95% CI 0.33-0.49). The clinical characteristics of patients with COVID-19 associated with a higher risk of presenting ACS were: previous coronary artery disease, age ≥60 years, hypertension, chest pain, raised troponin, and hypoxemia. The need for hospitalization and admission to intensive care and in-hospital mortality were higher in cases than in control group A (adjusted OR aOR 6.36 95% CI 1.84-22.1, aOR 4.63 95% CI 1.88-11.4, and aOR 2.46 95% CI 1.15-5.25). When comparing cases with control group B, the aOR of admission to intensive care was 0.41 (95% CI 0.21-0.80), while the aOR for in-hospital mortality was 5.94 (95% CI 2.84-12.4). The incidence of ACS in patients with COVID-19 attending the emergency department was low, around 1.48%, but could be increased in some circumstances. Patients with COVID-19 with ACS had a worse prognosis than control subjects with higher in-hospital mortality.