OBJECTIVE To investigate the relationship between the ABO blood group and the COVID-19 susceptibility. DESIGN The study was conducted by comparing the blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. Data were analyzed using one-way ANOVA and 2-tailed χ2 and a meta-analysis was performed by random effects models. SETTING Three tertiary hospitals in Wuhan and Shenzhen, China. PARTICIPANTS A total of 1,775 patients with COVID-19, including 206 dead cases, from Wuhan Jinyintan Hospital, Wuhan, China were recruited. Another 113 and 285 patients with COVID-19 were respectively recruited from Renmin Hospital of Wuhan University, Wuhan and Shenzhen Third People's Hospital, Shenzhen, China. MAIN OUTCOME MEASURES Detection of ABO blood groups, infection occurrence of SARS-CoV-2, and patient death RESULTS The ABO group in 3694 normal people in Wuhan showed a distribution of 32.16%, 24.90%, 9.10% and 33.84% for A, B, AB and O, respectively, versus the distribution of 37.75%, 26.42%, 10.03% and 25.80% for A, B, AB and O, respectively, in 1775 COVID-19 patients from Wuhan Jinyintan Hospital. The proportion of blood group A and O in COVID-19 patients were significantly higher and lower, respectively, than that in normal people (both P < 0.001). Similar ABO distribution pattern was observed in 398 patients from another two hospitals in Wuhan and Shenzhen. Meta-analyses on the pooled data showed that blood group A had a significantly higher risk for COVID-19 (odds ratio-OR, 1.20; 95% confidence interval-CI 1.02~1.43, P = 0.02) compared with non-A blood groups, whereas blood group O had a significantly lower risk for the infectious disease (OR, 0.67; 95% CI 0.60~0.75, P < 0.001) compared with non-O blood groups.In addition, the influence of age and gender on the ABO blood group distribution in patients with COVID-19 from two Wuhan hospitals (1,888 patients) were analyzed and found that age and gender do not have much effect on the distribution. CONCLUSION People with blood group A have a significantly higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O has a significantly lower risk for the infection compared with non-O blood groups.