BackgroundFatigue driving is a leading cause of traffic fatalities and injuries in China, especially among heavy truck drivers. The present study tried to examine which and how factors within the human-vehicle-roadway-environment system contribute to the occurrence of crashes involving fatigued truck drivers.FindingsTo reduce such risk on the road, a total of 9168 crashes which occurred in Jiangxi and Shaanxi between 2003 and 2014 were selected to measure the effects of potential factors on fatigue related truck crashes using a case control study. Pearson Chi-square test was used to determine the relationship between crash risk and independent factors, and a stepwise logistic regression model was developed to determine the significant risk factors. According to the data analysis results, driver’s gender, age, driving experience, and overspeeding behavior, vehicle’s commercial status, overloading conditions and brake performance, road’s type, slippery pavement and existence of sharp curve and long steep grade, and time of day, season, weather and visibility conditions, etc. were identified to be significantly associated with fatigue related truck crashes on Jiangxi and Shaanxi highways. Moreover, it is found that (a) in Jiangxi, an employed truck driver has a higher risk of crash involving multi-vehicles or a passenger car at bridge locations, and (b) in Shaanxi, the adult, tunnel location, summer and winter days prohibit statistically significant association with the occurrence of multi-vehicle and single-vehicle run-off-road/rollover crashes.ConclusionsYoung employed male truck drivers with less experience are at high risk, especially while driving across sharp curves, down long steep grades, over bridge or through tunnels, during the midnight period, on rainy, snowy or foggy days in rural areas. All these help recommend potential policy initiatives as well as effective safety promotion strategies at the public health scale for professional truck drivers.