Background: Traffic accidents with about 1.24 million deaths and 20 to 50 million cases of injury or disability per year are one of the most important public health challenges around the world. In Iran, traffic accidents, with an annual incidence of 32 cases per 100 thousand people, are considered as the second leading cause of death and the most common cause of injury. Objectives: This study aimed to evaluate the epidemiological pattern and mortality rate caused by traffic accidents during year 2012 in the Khuzestan province and its cities. Materials and Methods:In this cross-sectional study, all data related to fatal traffic accident referrals to legal medicine center of Khuzestan province during year 2012 were obtained and analyzed. Road traffic accidents mortality rate during this year was calculated for the province and its cities. The data were analyzed using Stata 11 statistical software. Results: In 2012, one thousand and twenty deaths related to traffic accidents occurred in Khuzestan province. The incidence of deaths due to accidents in Khuzestan province was 22.5 and the standardized age of incidence was 24.3 per 100 thousand people. Regarding gender, 78.24% of the dead individuals were male and 21.76% were female. The most common final causes of death were head trauma (76.27% cases) and bleeding (12.55% cases). The most deceased people were drivers (42.55%), passengers (34.90%), and pedestrians (21.27%). The highest traffic accidents mortality rate in Khuzestan province was observed in Hoveizeh (55.43 per one hundred thousand), Omidiye (55.30 per one hundred thousand) and Ramhormuz (53.12 per one hundred thousand), and the lowest incidence rates belonged to Lali (5.35 per one hundred thousand) and Shadegan (9.78 per one hundred thousand). Conclusions: This study showed that drivers, passengers and pedestrians were the most vulnerable road users. Regarding the fact that most of them were illiterate or had primary education and were self-employed or laborers, it seems essential to develop plans not only to train the road users but also to evaluate the safety of vehicles and roads and post-accident care programs, and consequently, implement special programs fully and strictly in order to reduce traffic fatalities.