The scope of this study was to describe the magnitude and distribution of deaths by homicide in the Americas and to analyze the prevailing trends. Deaths by homicide (X85 to Y09 and Y35) were analyzed in 32 countries of the Americas Region from 1999 to 2009, recorded in the Mortality Information System/Pan American Health Organization. A negative binomial model was used to study the trends. There were around 121,297 homicides (89% men and 11% women) in the Americas, annually, predominantly in the 15 to 24 and 25 to 39 year age brackets. In 2009 the homicide age-adjusted mortality rate was 15.5/100,000 in the region. Countries with lower rates/100,000 were Canada (1.8), Argentina (4.4), Cuba (4.8), Chile (5.2), and the United States (5.8), whereas the highest rates/100,000 were in El Salvador (62.9), Guatemala (51.2), Colombia (42.5), Venezuela (33.2), and Puerto Rico (25.8). From 1999-2009, the homicide trend in the region was stable. They increased in nine countries: Venezuela (p<0.001), Panama (p<0.001), El Salvador (p<0.001), Puerto Rico (p<0.001); decreased in four countries, particularly in Colombia (p<0.001); and were stable in Brazil, the United States, Ecuador and Chile. The increase in Mexico occurred in recent years. Despite all efforts, various countries have high homicide rates and they are on the increase.