Background: Motorcycles are the most popular vehicles in Taiwan, where more than 14.8 million motorcycles (1 motorcycle per 1.6 people) are in service. Despite the mandatory helmet law passed in 1997, less than 80% of motorcyclists in Taiwan wear helmets. Objective: The objective of this study was to analyze the effect of using motorcycle helmets on fatality rates. Methods: A clinical data set including 2,868 trauma patients was analyzed; the cross-sectional registration database was administered by a university medical center in Central Taiwan. A path analysis framework and multiple logistic regressions were used to estimate the marginal effect of helmet use on mortality. Results: Using a helmet did not directly reduce the mortality rate but rather indirectly reduced the mortality rate through intervening variables such as the severity of head injuries, number of craniotomies, and complications during therapeutic processes. Wearing a helmet can reduce the fatality rate by 1.3%, the rate of severe head injury by 34.5%, the craniotomy rate by 7.8%, and the rate of complications during therapeutic processes by 1.5%. These rates comprise 33.3% of the mortality rate for people who do not wear helmets, 67.3% of the severe head injury rate, 60.0% of the craniotomy rate, and 12.2% of the rate of complications during therapeutic processes. Discussion: Wearing a helmet and trauma system designation are crucial factors that reduce the fatality rate.