Background and aims: Road traffic accident annually lead to the death of 1.2 million people and also the disability of some 50 million people in the world. Iran is one of the countries with the highest rates of road accidents in the world. According to the annual statistics by the Iranian Legal Medicine Organization, 15,932 people have lost their lives in road traffic accidents in 1395 sh. According to figures in this report, over 75% of road deaths occur among men. Driving and guiding a vehicle is required to assign different levels of attention. In this regard, also can be pointed to the role of the mental workload. Mental workload known as a requirement that a duty impose on the available mental and cognitive resources of people. Mental workload is too high or too low can lead to incomplete understanding, inadequate attention and information processing to be inappropriate. A variety of factors can be effect on individuals driving performance and their mental workload such as age, gender, driving character and fatigue. According to studies, mistakes that can lead to accidents, in many cases, are the result of high mental workloads. Measurement of mental workload while driving can reflect the cognitive needs imposed on the driver. Various behavioral, self-reporting and physiological methods have been successfully used so far in order to measure the mental workload. One of the best ways to measure the mental workload is the evaluation of the individualschr('39') reaction time. Reaction time is the time interval between the emergence of a stimulus and the individualchr('39')s response. Driver’s gender is one of the possible effective factors that can affect driving performance. This study aimed to assess the effect of gender on young driverschr('39') mental workload and driving performances using a driving simulator. Methods: This cross-sectional study was conducted on 40 young drivers (20-29 years) including 20 women and 20 men in Tehran at 2017. The inclusion criteria for the study were aged 20 to 29 years, filling informed consent to participate in the study, sleeping enough for 8 hours at night before the test, having at least two years of driving experience, driving at least once In the week, lack of driving experience with the driving simulator, having adequate or improved vision for the eyes, or for each eye, did not use psychotropic drugs. Exclusion criteria were included the request of the participants to leave the study, having signs of discomfort caused by the simulator, expressing a physical discomfort after the start of the test for any reason. The driving simulator used in this study is a half-body Pride made by the specialists of the virtual reality group of Khajeh Nasir Tusi Industrial University. The simulator has a computer and graphics card and software tools for simulating intra-city and inter-city roads, freeways, night driving, and driving in snowy, rainy, and foggy conditions. The driverschr('39') performances were evaluated using the PDT reaction time and vehicle lateral deviation variables under two conditions: driving with and without mental calculations. The PDT reaction time test is one of the most common and suitable methods for assessing the performance of drivers and the response time of mental workload in simulator studies. Its validity and reliability have been confirmed in various studies. The Rating Scale Mental Effort (RSME) and the Integrated Workload Scale (IWS) self-report scales were used to estimate the individualschr('39') workload. The main scenario of the study included driving a distance of 20 km on a highway. Results: The mean lateral deviation obtained for female and male drivers was 0.55 and 0.51 m respectively, in the driving phase without mental calculations. Moreover in this phase the mean reaction time was 482 ms for females and 450 ms for males. In the driving phase with mental calculation, the mean lateral deviation obtained for female and male drivers was 0.67 and 0.62 m and mean reaction time for females and males was 606 ms and 569 ms, respectively. Based on the RSME and the IWS scales, women perceived more mental workload than men. For most variables of the study, however, the difference between male and female values was not significant based on the independent t-test (P-value> 0.05). Also, performing mental calculations while driving caused a significant increase (P-value = 0.05) in the values of the vehiclechr('39')s lateral deviation, the driverschr('39') reaction time, and the RSME and the IWS scales. Conclusions: Although there were no statistically significant differences in the study variables between males and females; the mean value of the lateral deviation for women was slightly higher than men, and their driving performance was slightly weaker than men. More lateral deviation of the vehicle should be considered in the process of doing mental calculation, because the high lateral deflection, especially automotive deviation to the left can be dangerous and even fatal accidents.