Injuries, disabilities and deaths among motorcyclists have been rising worldwide but what is happening in the American Continent is not completely known. Deaths from motorcycle crashes of the Pan American Health Organization database (PAHO/WHO, 1998–2010) were included in an ecologic multi-national study to quantify the temporal trends and to estimate the association between motorcycle riders' deaths and selected socio-economic indicators. Mortality rates increased in all sub-regions. The highest increase was reported in the countries of the Andean sub-region (Ecuador, 78.3%) and Mesoamerica (Costa Rica, 60.0%). Poorer countries fared worse in terms of motorcycle mortality relative to richer countries, as did more unequal ones. Recent economic changes, rapid increment of motorisation rates, affordability of motorcycles over public transportation, lack of adequate public transportation policies and other insufficient measures aimed at improving safety can explain these trends.