Traffic accidents are the third largest cause of death according to the World Health Organization. Moreover, driver fatigue is the second largest factor that causes traffic accidents after traffic violations. The purpose of this study is to find out the significance of driver fatigue using physiological, cognitive, and subjective approaches, as well as a comparison of fatigue between male and female drivers. The study involved twelve respondents, which included six male respondents and six female respondents aged 17−25 years old, measured by physiological (blood pressure and heart rate), cognitive (psychomotor vigilance test), and subjective (Karolinska Sleepiness Scale) approaches. The result of this study is that heart rate is the most sensitive variable. However all of the variables in male and female respondents do not have a significant result. There is no big difference in fatigue levels in male and female car drivers. The conclusion of the study is that the approaches could not be a standardized way to measure fatigue for male and female car drivers because of the variation in results.