An enforcement emphasis project, “Operation Trucker Check,” was established in order to determine the extent to which commercial tractor-trailer drivers were operating their vehicles while impaired by drugs. A total of 1079 drivers and their vehicles were assessed for driver and equipment violations, and drivers additionally underwent preliminary field sobriety tests conducted by drug recognition expert (DRE) officers. Anonymous urine specimens for drug analysis were requested, and 822 urine specimens were obtained in total. Compliance with the drug-testing portion was voluntary, and there was a 19% refusal rate. Overall, 21% of the urine specimens tested positive for either illicit, prescription, and/or over-the-counter drugs, and 7% tested positive for more than one drug. Excluding caffeine and nicotine, the largest number of positive findings (9.5%) were for CNS stimulants, such as methamphetamine, amphetamine, phentermine, ephedrine/pseudoephedrine, and cocaine. The second most frequently encountered drug class were the cannabinoids, with 4.3% of drivers testing positive for marijuana metabolites. Only 11 drivers (1.3%) were positive for alcohol. Sixteen truck drivers (1.6%) were charged with driving under the influence of drugs after a full DRE evaluation was conducted. The results indicate that in spite of comprehensive drug testing in the trucking industry, some tractor-trailer drivers are continuing to take illicit and other drugs with the potential of having a negative effect on their driving ability. On the other hand, only a few drivers were, in fact, deemed to be under the influence of drugs at the time of driving when evaluated by DRE officers.