Highlights  The toxicological findings in driver and motorcycle fatalities in Scotland have been examined. Fifty-seven percent of the cases examined were positive for drugs and/or alcohol. The most common findings were alcohol and cannabinoids. AbstractFatal motor vehicle crashes (MVCs) continue to be a common occurrence worldwide. This paper presents a retrospective analysis of the toxicological investigation of drivers and motorcyclists fatally injured in MVCs in Scotland from 2012 to 2015. One hundred and eighteen cases with full toxicological analysis, i.e., alcohol, drugs of abuse and prescription drugs, were examined. Of those 118 MVC cases, 74 (63%) were car drivers, 32 (27%) were motorcyclists and the remaining were drivers of other vehicles such as large goods vehicles. The majority of deceased drivers and motorcyclists were male (N = 104, 88%). For the toxicological findings, 51 (43%) were negative, and of the 67 (57%) positive cases, alcohol and cannabinoids were the most frequently detected substances, followed by opiates and benzodiazepines. Fifteen percent of all drivers and motorcyclists were over the prescribed blood alcohol limit at the time of analysis. In comparison to previous reports