In order to assess the potential benefit in human lives if all geographical regions in the US (Northeast, South, Midwest, and West) achieved the lowest suicide and homicide rates observed within these regions, age-, race- and gender-adjusted suicide and homicide rates for each of the four regions were calculated based on data retrieved using the Centers for Disease Control and Prevention database for 1999-2004. Data on known risk factors were retrieved from online sources. Overall suicide rates (10.42 per 100,000) exceeded homicide rates (6.97 per 100,000). Almost 27% (12,942 lives per year) of the 288,222 suicide and homicide deaths during the study period might have been avoided if all US regions achieved the mortality rate reported by the Northeast. A firearm was used in 55% of all suicides and 66% of all homicides. In the total estimate of avoidable deaths, firearm suicides (90%) and firearm homicides (75%) were overrepresented. The Northeast had the lowest access to firearms (20%) contrasted to almost double in the other regions, whereas greater firearms availability was related to unrestricted firearm legislation. Measures to restrict firearms availability should be highly prioritized in the public health agenda in order to achieve an impressive benefit in human lives.