Rationale: Adverse drug effects such as reduced alertness may cause drivers to be unaware that their driving is impaired. Objective: This study was conducted to examine if drivers are adequately aware of their driving ability when treated with central nervous system drugs. Methods: Data from three clinical trials applying the on-the-road driving test were used to compare the primary outcome measure, the Standard Deviation of Lateral Position, with subjective assessments of alertness before driving, as well as perceived driving quality, and mental effort to perform the test. Results: The analyses revealed significant correlations for perceived driving quality (r = -0.498, p < 0.0001), mental effort to perform the test (r = 0.408, p < 0.0001), and alertness taken before driving (r = -0.115, p < 0.017). The predictive validity (R 2) of perceived driving quality (24.8%), mental effort (16.6%), and alertness before driving (1.3%) was low. Conclusion: The analyses show that subjective assessments do not robustly relate to actual driving performance either in terms of judgments about alertness before the drive or ratings of performance after the drive.