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Background:: Motor vehicle crashes (MVC) are considered to be the most common safety challenge, causing more than a million deaths worldwide annually. Objectives:: The current study was aimed at identifying the etiological role of human and vehicle safety factors in road crashes, and their effects on the severity of injury and fatality in the Sistan and Baluchistan Province, South East Iran. Patients and Methods:: In this study, 2 703 MVC recorded at the police office during one year period, were reviewed. The profile of the crashes was comprised of data that included; demographic characteristics of the injured persons in a MCV, type of crash, type of vehicles involved, location of crash, as well as human, environmental and mechanical factors which contributed to the crash. Data were analysed using binary and multinomial logistic regressions. Results:: After adjusting for confounding factors, vehicles with passengers were 33% more likely to have a crash. Furthermore, pickup trucks and heavy trucks increased the chance of causing a crash, 1.66 and 1.84 times more than saloon cars, respectively. Vehicles made after 2005 had twice the risk of causing a crash than those made in 1980 or before. In addition, in a multivariate model; drivers age, type of vehicle and circumstances of car damage were contributing factors to the severity of injury. Conclusions:: Type and age of the car, the presence of passengers and the degree of damage to the car were the determinant factors for car crashes, and consequent severity of injury in the study area. Educational programs must be directed at promoting public knowledge about the consequences of their behavior as either a passenger or driver.