OBJECTIVE: To identify determinants of regional differences in traffic accident mortality in Italy. DATA AND METHODS: Multiple linear regression models were conducted assessing the associations between regional differences in traffic mortality, case fatality and accident rates (dependent variables) with socio-demographic factors, and variables describing road behaviour, vehicles, infrastructure and medical care (independent variables). Data were derived from the National Institute of Statistics, the National Institute of Health and the Italian Automobile Club. In addition to analyses for the whole country of Italy, separate models were conducted for Northern and southern regions. RESULTS: In Italy large regional differences in traffic mortality rates can be observed, ranging from 5.5 to 20 per 100.000 person-years. There is a North-South gradient with higher mortality rates in the Northern part of Italy. Strong predictors of regional differences in both traffic mortality and accident rates are the employment rate (directly associated) and alcohol use (directly associated). This is observed in the whole of Italy, and separately in Northern and southern regions. CONCLUSION: Our study has shown the need for regional policies to improve road behaviour to reduce traffic accident and mortality rates in identified high-risk areas.