BACKGROUND: The infant mortality rate (IMR) is a proxy of the living and health conditions of a given population, which allows us to assess the risk of death for children under one year. Although there is, in general, a reduction in infant mortality in Brazil little is known about this indicator in the regions and cities located on the international borders of the Brazilian territory and the changes that occurred in the face of the migratory impact of the Americas in the period from 1996 to 2020. The objectives of this study are to assess IMR in Brazilian Twin Cities (municipalities that are located on the border with a large influx of people) and its social determinants over time. METHODS: This is an ecological study, whose units of analysis were the Brazilian Twin Cities, between 1996 and 2020, based on data on births and deaths in children under one year, available in the public vital information system in Brazil. Data were identified by the city in which the infant death occurred in addition to the mother's primary city of residence. Correlation measurements were performed to test the associations of the IMR means between the independent variables. RESULTS: The Twin Cities (Bonfim, Tabatinga, Pacaraima, Porto Murtinho, Cáceres, Foz do Iguaçu, Santo Antônio do Sudoeste e Dionísio Cerqueira) had higher numbers of infant deaths per place of occurrence than the number of deaths per place of maternal residence. The Northern Twin Cities exhibited the highest IMRs. Cities in the Midwest region showed variability. In the South region, most cities showed low rates. A positive correlation was identified with the Gini index with r = 0.67 and a negative correlation with the Municipal Human Development Index indicator of r= -0.70. CONCLUSIONS: The averages of IMRs in the Twin Cities were higher than in their States. In recent years, there has been an upward trend in infant mortality in these cities.