Introduction: The COVID-19 pandemic has been variable, the application of vaccines has modified the behavior of the disease, persisting as a great threat to health. Objective: To describe the behavior of COVID-19 after vaccination in Tlaxcala, Mexico. Methods: Observational, descriptive, study. Prior approval by the local investigation committee, the record of patients with a positive rapid test or PCR for COVID-19 and at least one dose of the vaccine between March and October 2021 was reviewed. General data related to the disease and the vaccine were analyzed. A descriptive analysis and chi-square, Fisher's exact test, linear association, Mann-Whitney U test. SPSS program. Results: It included 2037 records, 50% women, median age 38 years, 17% had sudden onset of symptoms, 43% had a complete vaccination schedule, there were from 5 to 286 days between the first dose of vaccine and onset of clinical symptoms, 6% required hospitalization, 2% died (with a significant difference about comorbidities, the time between application and onset of symptoms and vaccination status). Conclusions: There is no difference in the behavior of COVID-19 with the vaccine brand, sex, or age, with a low frequency of hospitalization and mortality, associated with the number of comorbidities and vaccination schedule.