Objectives: Droperidol (DROP) is used in the emergency department (ED) for several indications, but its effect on psychomotor performance is unclear. The purpose of this study was to evaluate the effects of DROP, 2.5 mg intramuscular (IM), on driving performance.Methods: This was a randomized, double-blinded, two-period, placebo-controlled crossover trial that utilized a standard drivertraining program with computerized scoring. We solicited 20 paid volunteers who were pre-screened with a 12-lead EKG to evaluate QT length. For the first driving simulation, subjects were randomly assigned to receive either 2.5 mg of DROP IM or an equal volume of normal saline (NS). At least 72 hours later, the same subjects participated in a second driving simulation. For the second driving simulation, the assignment of DROP, 2.5 mg IM, or normal saline was reversed: (If a subject received DROP, 2.5 mg IM, in the first simulation, the subject received normal saline in the second simulation; conversely, if a subject received normal saline in the first simulation, the subject received DROP, 2.5 mg IM, in the second simulation). Thirty minutes later, participants drove the 20-minute simulation and received an average score based on the errors made in 4 categories: accelerating, braking, steering, and signaling. Post-testing, participants evaluated their degree of drowsiness and driving impairment using a visual analog scale and compared their perception of impairment to that caused by alcohol ingestion. Data were analyzed using analysis-of-variance, Pearson chisquare and Fischer's exact test with alpha set at p = 0.05.Results: Twenty subjects (11 males and 9 females) completed the protocol. The mean age was 30 years with a range of 20 to 46 years, and the mean weight was 80 kg. The mean driving experience was 12 years. Participants who received DROP felt significantly drowsier (38.6 mm +/− 9.0) than those receiving NS (13.2 mm +/− 9.0), the mean difference was 25.4 mm p = .009. Subjects receiving DROP were also more likely to feel that their driving would be impaired as rated on the VAS (DROP: 34.6 +/− 5.2; NS: 3.2 +/− 5.2; p = .0005), and DROP subjects reported impairment equivalent to 1-4 drinks more frequently than those receiving placebo (61% vs. 16.7%, p < .001). These subjective feelings of impairment were confirmed by their driving performance on the simulator. The mean driving score, using the driving simulator, was 68.8% with DROP vs. 73.6% with NS; p = .013.Conclusions: Subjects receiving modest doses of IM DROP report increased perceptions of drowsiness, driving impairment, and intoxication; these perceptions are confirmed on objective testing.