Our objective was to determine the presence of psychoactive substances in blood of drivers killed in road crashes in four European countries. Data from 1118 drivers of car and vans, killed between 2006 and 2009, were collected in Finland, Norway, Portugal and Sweden. The prevalence of any psychoactive substance ranged between 31 and 48%. Alcohol (≥ 0.1 g/L) was the most common finding, 87% had a blood alcohol concentration (BAC) ≥ .5 g/L. Benzodiazepines (1.8-13.3%) and amphetamines (0-7.4%) were the most prevalent psychoactive medicines and illicit drugs, respectively. Alcohol-drug and drug-drug combinations were rather prevalent. Differences in alcohol/drug findings seemed to reflect differences in use in the countries. More research should be done to develop preventive strategies to reduce the number of alcohol- and drug-related traffic accidents targeting at-risk groups, such as drivers with very high BACs and novice drivers.