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The COVID-19 pandemic has had a major impact on human health around the world. Given the speed of the spread of the disease and its impact on people’s lives, different countries including Jordan issued approval for the emergency use of the mRNA vaccine BNT162b2 for COVID-19. This respiratory disease has led to an increased risk of complications and significant mortality in patients with pre-existing medical conditions such as respiratory disease, cardiovascular disease, and diabetes. Vaccination against COVID-19 is recommended for people with chronic diseases to reduce the risk of infection, hospitalization, and death. The BNT162b2 vaccine has shown high efficacy in healthy adults. The results of our study suggest a high efficacy of the BNT162b2 vaccine in patients with diabetes and cardiovascular after the second and third doses compared to the first dose of the vaccine. Vaccine efficacy for the third dose was similar to that for the third dose while the effectiveness did not change between the first, second, and third doses in respiratory diseases. In conclusion, receiving second and third doses of the COVID-19 vaccine was associated with a decreased risk of mortality and hospitalization compared with the first dose. Unfortunately, the efficacy of the first, second, and third doses was similar in respiratory patients.