Objectives: Since its appearance in 2019, multiple risk factors have been identified for presenting a severe form of COVID-19 and different vaccines have also been developed to prevent severe manifestations. However, despite a vaccination history, some cases progress to complications or even death. The objective of this study was to determine the strength of the association between the severity of COVID-19 and the history of vaccination in patients treated at a public reference hospital in Mexico City. Methods: This was a non-experimental, retrospective, and analytical epidemiological study of cases and controls. The study population was people treated at a concentration hospital for COVID-19 care between July 1, 2021, and June 30, 2022, in Mexico City. Results: 132 participants (44 cases and 88 controls) were included in the study. The risk factors most strongly associated with COVID-19 severity were age greater than or equal to 60 years, presenting 22 breaths per minute at the first medical evaluation, systolic blood pressure greater than or equal to 140 millimeters of mercury, and a history of at least one chronic comorbidity. However, vaccination history was associated with 94% (OR 0.06) lower odds of developing severe COVID-19 compared to those without a history of vaccination, regardless of the presence of associated risk factors. Conclusion: Lacking a history of vaccination and presenting any of the identified risk factors confer higher odds of developing severe forms of the disease.(AU)