The present study was aimed at determining whether drivers testing positive for drugs and/or alcohol were more often responsible for the crash than the test-negative ones. Data on 241 fatally injured and 102 hospitalized motor-vehicle drivers was collected in Northern and Western Sweden. Blood samples were taken from these drivers and screened for the presence of alcohol, licit drugs, and illicit drugs. A judgment of responsibility, and assessment of the traffic situation and crash characteristics were based on police reports. Alcohol-positive drivers (n = 49) were more often (96% vs. 70%, p < 0.0001) judged to be responsible for the crash than test-negative drivers. Ninety-three percent of the drug-positive drivers were judged to be responsible, but they were not significantly more often responsible than the test-negative drivers. Drug-positive drivers differed from the alcohol-positive drivers in that they more often crossed over to the wrong side of the road and crashed into an oncoming vehicle. The findings support previous studies that reducing the number of drug-positive drivers in traffic is bound to lead to a reduction in crashes resulting in injury. Further analysis with a larger sample is needed to elucidate the association between crash responsibility and drugs other than alcohol.