Since 2021, the activity and impact of the highly pathogenic H5N1 avian influenza virus have intensified worldwide, causing high mortality in wild birds and birds while also infecting various wild and domestic mammals and humans. Particularly, the severe impact on commercial poultry farming has prompted various countries to implement control and mitigation plans to address the damage caused by these viruses. In Mexico, the implementation of vaccination was part of the comprehensive strategies to prevent and control highly pathogenic H5N1 avian influenza outbreaks. For this reason, this work aimed to compare antibody levels in production birds before and after vaccination, examining seroconversion and seroprotection after vaccination in two time periods. Serum samples were taken before and after vaccination in 573 Poultry Production Units during the first vaccination period and 205 Poultry Production Units during the second period across various Mexican states. These samples, later, underwent hemagglutination inhibition tests. With the results obtained from serology, comparisons of medians, calculations of seroconversion and seroprotection, as well as logistic regression analysis were performed. As expected, vaccination led to a statistically higher immune response in birds in most of Mexico´s states. However, seroconversion and seroprotection rates remained below 80?% during the first evaluation period. Progenitors and commercial posture birds showed better immune responses to vaccination, particularly with vaccines developed through reverse genetics. These results provide valuable insights into the immune response of Mexican domestic birds under the national strategic plan to control the highly pathogenic influenza A H5N1 virus emergency, which will set a precedent to improve the prevention and control of future outbreaks.