This study compared risk factors for infant mortality in 2000-2001 and 2007-2008 in Londrina, Paraná State, Brazil. Data on live births and infant deaths were linked in a single database, and a hierarchical regression model was used. Distal risk factors for infant mortality in 2000-2001 were maternal age < 20 or ≥ 35 years and lower maternal schooling. In 2007-2008, maternal age ≥ 35 or < 20 years were risk factors, while low schooling appeared as a protective factor. The following intermediate factors were associated with increased infant mortality in 2000-2001: multiple pregnancy, history of stillbirth, and insufficient number of prenatal visits, while cesarean delivery was a protective factor. Multiple pregnancy was the only intermediate risk factor in 2007-2008. All of the proximal factors were associated with higher infant mortality in 2000-2001, but only gestational age and 5-minute Apgar in 2007-2008. The risk factors for infant mortality changed from the first to the second cohort, which may be related to the expansion of social policies and primary care and changes in the reproductive and social patterns of Brazilian women.