OBJECTIVE: We aimed to compare the effects of blood groups and Rh factor on the development of coronavirus-19 disease (COVID-19) with all aspects such as clinical course, inflammatory parameters, and organ-specific biochemical parameters with a significant number of patients. METHODS: This multicenter study was carried out retrospectively on 3551 patients hospitalized with the diagnosis of COVID-19 and whose blood groups were recorded during the time of hospitalization. As control groups, 22133 individuals' medical data who were admitted to the blood bank affiliated with our hospitals during the last year was used. The differences between the blood groups and clinical characteristics were analyzed. RESULTS: Of the 3551 patients, A Rh (+) blood group was found to be in a higher ratio in the case group than controls, with increased risk to be infected (case: 41.3% vs. control: 38.8%), (OR 1.113; 95% CI: 1.036-1.197; p=0.003). Meanwhile O Rh (+) blood group ratios were significantly lower in the case group than in the control group (case: 26% vs. control: 28.3%) (OR 0.862; 95% CI: 0.823-0.966; p=0.005). There was no significant difference between blood groups in terms of admission to the intensive care units and mortality, it was observed that patients with AB Rh (+) blood group have a greater risk for intubation than others (OR: 1.467; 95% CI: 1.040-2.071; p=0.028). CONCLUSION: We demonstrated that people with blood group A Rh (+) more susceptible to COVID-19, whereas blood group 0 Rh (+) have a protective effect against the infection. Once a person has been infected with severe acute respiratory syndrome coronavirus 2, we should be mindful that patients with blood group AB Rh (+) would be prone to intubation more than other blood groups.