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Purpose The coronavirus disease 2019 (COVID-19) pandemic has shown unprecedented impact world-wide since the eruption in late 2019. Importantly, emerging reports suggest an increased risk of thromboembolism development in patients with COVID-19. Meanwhile, it is found that aspirin reduced mortality in critically ill patients with non-COVID-19 acute respiratory distress syndrome. Therefore, a meta-analysis was performed to investigate the effects of aspirin on COVID-19 mortality. Methods A systematic literature search was conducted in 10 electronic databases and 4 registries. Random effects models were used to calculate pooled relative risks (RRs) with 95% confidence intervals (Cis) to estimate the effect of aspirin on COVID-19 mortality. Relevant subgroup analyses and sensitivity analyses were also performed. Results The results showed that aspirin use was associated with a reduction in COVID-19 mortality (adjusted RR 0.69; 95% CI 0.50–0.95; P < 0.001). Subgroup analysis found that the low-dose group was associated with a reduced COVID-19 mortality (adjusted RR 0.64; 95% CI 0.48–0.85; P < 0.01). Aspirin use was associated with reduced COVID-19 mortality in Europe and America (crude RR 0.71; 95% CI 0.52–0.98; P = 0.04), and results from cohort studies suggested that aspirin use was a protective factor for COVID-19 mortality (adjusted RR 0.73; 95% CI 0.52–0.99; P = 0.04). Meanwhile, aspirin use was not associated with bleeding risk (crude RR 1.22; 95% CI 0.80–1.87; P = 0.96). Conclusions This meta-analysis found that aspirin use was associated with a reduction in mortality in patients with COVID-19 and not with an increased risk of bleeding. Supplementary information The online version contains supplementary material available at 10.1007/s00228-022-03356-5.

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