Road accidents are the leading type of work-related fatalities, but the impact of work-related travel on overall traffic safety has been scarcely studied. The main objective of the present study was to assess drivers' relative road accident risk between work-related and personal journeys. A responsible/non-responsible case-control study was performed on a sample of 7,051 road accidents in France from the VOIESUR project. Logistic regression determined odds-ratios according to work-related versus personal travel, and identified risk factors for responsibility, specific to each of the two sub-groups. Drivers traveling on duty or commuting home were significantly less often responsible for accidents than drivers on personal journeys: OR = 0.75 [0.63; 0.89] and 0.65 [0.53; 0.80] respectively. Responsibility was significantly more frequent in commuting to versus from work: OR = 1.38 [1.06; 1.78]. Among on-duty drivers, professional passenger-transport drivers had the lowest risk of responsibility (OR = 0.25 [0.11; 0.58]), while those on temporary or work/study contracts and professional light goods vehicle drivers had the highest risk (OR = 11.64 [2.15; 62.94] and OR = 29.83 [5.19; 171.38] respectively). When driving under the influence of alcohol, risk of responsibility was higher in commuting home than in personal journeys. On-duty drivers showed lower risk of responsibility for an accident than other drivers. However, on-duty drivers on temporary or work/study contracts, who are usually not subject to specific regulations, showed higher risk, and should be the subject of particular attention regarding occupational risk prevention.