Our research aimed to describe infectious disease mortality in Italy between 1969 and 1999, with particular emphasis on sex, age, and geographic differences. Using mortality data provided by the Italian Central Institute for Statistics (ISTAT), we evaluated all codes of the ICD8 and ICD9 classifications to identify each cause of death attributable to infectious agents. Deaths for HIV/AIDS were excluded. Infectious diseases accounted for 1.7% of overall mortality between 1969-1999, and our approach identified 57.5% of all deaths from infections not included in the ICD8 and ICD9 infectious disease codes. Up to 1994, the mortality for all infectious diseases showed a very strong downward trend, with a 6-fold decline. This trend levelled off in 1995-1999, mainly due to increasing deaths due to septicaemias, heart infections and hepatitis. An increasing proportion of deaths due to infectious diseases occurred in the elderly, from 48.1% in 1969-1979 to 77.3% in 1990-1999. Mortality rates were consistently higher in men than in women and showed a substantial geographic heterogeneity. In the newborn, mortality rates declined 10-fold and an inverse north-south geographic gradient persisted during the study period. This exhaustive methodological approach to identifying infectious causes of deaths allows us to better define the burden of infections on mortality and register downward trends similar to those found in other industrialized countries.