To assess the relationship between real and simulated driving performance and the objective level of alertness as measured by the Maintenance of Wakefulness Test (MWT) in patients suffering from narcolepsy or idiopathic hypersomnia. Twenty-seven patients (10 patients with narcolepsy, type 1 (n = 7) and type 2 (n = 3), and 17 patients with idiopathic hypersomnia, mean age = 33.8 ± 11.1 years, range = 18-65 y; four males) were recruited in a randomized, crossover, double-blind placebo-controlled trial, and compared to 27 matched healthy controls. Patients were randomly assigned to receive modafinil (400 mg) or placebo before the driving test (2 h of real and 2 h of simulated highway driving for each patient). Standard deviation of lateral position (SDLP) of the vehicle in real and simulated driving and mean sleep latency in a 4 × 40 min MWT were assessed. Untreated patients presented shorter sleep latencies on the MWT (20.8 (IQ range 16.1-32.9) vs. 34.9 min (IQ range 28.1-40.0)) and worse simulated driving performance (P < 0.001) than treated patients. Nevertheless, treated patients still exhibited shorter mean sleep latencies on the MWT than controls (34.9 (IQ range 28.1-40.0) vs. 40 min (IQ range 37.1-40.0), P < 0.05), but driving performance was identical in both groups. The SDLP of the vehicle in real driving conditions and the MWT score correlated with the SDLP in simulated driving (respectively, r = 0.34, P < 0.05 and r = -0.56, P < 0.001). In patients with narcolepsy/idiopathic hypersomnia, simulated driving and MWT explore different dimensions of fitness-to-drive and could be used complementarily to better evaluate sleep-related driving impairment.Read less <