Purpose: To identify and appraise the published studies assessing interventions accounting for reducing fatigue and sleepiness while driving. Methods: This systematic review searched the following electronic databases: Medline, Science direct, Scopus, EMBASE, PsycINFO, Transport Database, Cochrane, BIOSIS, ISI Web of Knowledge, specialist road injuries joals and the Australian Transport and Road Index database. Additional searches included websites of relevant organizations, reference lists of included studies, and issues of major injury joals published within the past 15 years. Studies were included if they investigated interventions/exposures accounting for reducing fatigue and sleepiness as the outcome, measured any potential interventions for mitigation of sleepiness and were written in English. Meta-analysis was not attempted because of the heterogeneity of the included studies. Results: Of 63 studies identified, 18 met the inclusion criteria. Based on results of our review, many interventions in the world have been used to reduce drowsiness while driving such as behavioral (talking to passengers, face washing, listening to the radio, no alcohol use, limiting the driving behavior at the time of 12 p.m. - 6 a.m. etc), educational interventions and also changes in the environment (such as rumble strips, chevrons, variable message signs, etc). Meta-analysis on the effect of all these in-terventions was impossible due to the high heterogeneity in methodology, effect size and interventions reported in the assessed studies. Conclusion: Results of present review showed various interventions in different parts of the world have been used to decrease drowsy driving. Although these interventions can be used in countries with high incidence of road traffic accidents, precise effect of each intervention is still unknown. Further studies are required for comparison of the efficiency of each intervention and localization of each intervention ac-cording to the traffic patts of each country.