Aim: This study investigated whether the CHA2 DS2-VASC score is an independent predictor of high thrombus burden and mortality in patients presenting with acute coronary syndrome (ACS) and Coronavirus Ddisease (COVID-19). Materials and Methods: Patients with acute coronary syndrome (ACS) and COVID-19 (n = 76) were included in the study. They were categorized into low thrombus burden (LTB; grades 1–3) and high thrombus burden (HTB; grades 4 and 5) groups according to the final thrombus score. The CHA2 DS2-VASC scores were then compared between the two groups. Results: Post-procedural HTB developed in 50 patients (65.7%). The neutrophil-to-lymphocyte ratio (6.00 ± 3.73 vs. 11.45 ± 10.6; P < 0.05), creatinine (0.84 ± 0.22 vs. 1.51 ± 0.92 mg/dL; P < 0.05), blood urea nitrogen (42.27 ± 12.6 vs. 62.27 ± 48.2 mg/dL; P < 0.05), potassium (4.06 ± 0.35 vs. 4.51 ± 0.49 mEq/L; P < 0.05), ferritin (286 ± 55.2 vs. 730 ± 96.8 ng/mL; P < 0.05), interleukin-6 (18.12 ± 7.14 vs. 186.66 ± 56.8 pg/mL; P < 0.05), lactate dehydrogenase (425.7 ± 31.2 vs. 1002.7 ± 173.4 U/L; P < 0.05), and CHA2 DS2-VASC score (2.84 ± 1.27 vs. 4.08 ± 1.61; P < 0.05) were significantly higher in the HTB group. Mortality [3 (11.5%) vs 23 (46.0%), P<0.05)] and CHA2DS2-VASc score (2.84 ± 1.27 vs 4.08 ± 1.61, P<0.05) were higher in the HTB group (Table 1). Conclusions: In this study, the easily calculated CHA2 DS2-VASC score was an independent predictor of HTB in patients with COVID-19 presenting with ACS. In addition, it predicted mortality in the same patient group.