Acute COVID-19 infection is associated with increased adverse clinical outcomes in patients with acute coronary syndromes (ACS). Given that some studies suggested improved pulmonary function with Ticagrelor, this clinical trial aimed to compare the effects of Ticagrelor versus Clopidogrel on the short-term outcomes of these patients. In this multicenter clinical trial, 180 COVID-19 patients with ACS who underwent urgent percutaneous coronary intervention (PCI) were randomized to receive Ticagrelor (180mg loading dose followed by 90mg twice daily, n=90) or Clopidogrel (600mg loading dose with 75mg daily, n=90), and then followed for one month after their procedure. The primary composite endpoint was a combination of all-cause mortality, myocardial infarction, and early stent thrombosis within the first month after stent implantation. After thirty days of follow-up, the primary composite endpoint was non-significantly lower in the Ticagrelor compared to the Clopidogrel group (18.5% vs 23.5% respectively, p = 0.254). Based on the time-to-event analysis, the mean survival rate was 26.8 ±7.7 and 24.7 ±9.9 days, respectively, for the Ticagrelor and the Clopidogrel arms (Log-rank p = 0.275). Secondary endpoints were similar in the two trial arms, except for the mean oxygen saturation, which was higher in the Ticagrelor group (95.28 ±2.68 % vs. 94.15 ± 3.55 %, respectively; p = 0.021). Among COVID-19 patients with concomitant ACS, who were treated with urgent PCI, the composite outcome of death, myocardial infarction, and early stent thrombosis was not different between Ticagrelor and Clopidogrel groups. However, administration of Ticagrelor was associated with a slight but statistically significant increase in oxygen saturation compared to Clopidogrel, but this difference wasn't clinically important.