INTRODUCTION: Research shows the correlation between angiotensin-converting enzyme (ACE) deletion and insertion (D/I) polymorphism and COVID-19 risk; yet, conclusive evidence is still lacking. Thus, a meta-analysis of relevant articles was performed to more accurately estimate the relationship of ACE I/D polymorphism with the risk of COVID-19. . Relevant literature from the PubMed database was systematically reviewed, and odds ratios (ORs) and associated 95% confidence intervals (CIs) were measured. Additionally, the metapackage from Stata version 15.0 was used for statistical analysis. RESULTS: The meta-analysis eventually contained 8 studies, including 1362 COVID-19 cases and 4312 controls. Based on the data, the ACE I/D polymorphism did not show an association with COVID-19 risk (D vs. I: OR = 1.25, 95% CI = 0.96-1.64; DD vs. II: OR = 1.89, 95% CI = 0.95-3.74; DI vs. II: OR = 1.75, 95% CI = 0.92-3.31; dominant model: OR = 1.88, 95% CI = 0.99-3.53; and recessive model: OR = 1.24, 95% CI = 0.81-1.90). Further, subgroup analyses stratified based on case proved that the ACE D allele demonstrated an association with increasing risk of COVID-19 severity (D vs. I: OR = 1.64, 95% CI = 1.01-2.66; DD vs. II: OR = 4.62, 95% CI = 2.57-8.30; DI vs. II: OR = 3.07, 95% CI = 1.75-5.38; dominant model: OR = 3.74, 95% CI = 2.15-6.50; and recessive model: OR = 1.28, 95% CI = 0.46-3.51). CONCLUSIONS: The ACE D allele was clearly related to an enhanced risk of COVID-19 severity. Hence, it is imperative to take into account the influence of genetic factors during the development of future vaccines.