There are potential interactions among approaches to reduce or prevent certain accident causes. Given the overlapped safety benefits of various measures for accident prevention, it is necessary to identify their interactions and quantify the safety effectiveness of combined accident prevention strategies. This study focuses on strategies to prevent broken rails and broken wheels, respectively. Improved wheel condition reduces the impact load on the rail, thereby may reduce broken-rail-caused derailments. In this paper, we propose a quantitative framework to assess the safety effectiveness of combined accident prevention strategies under various operational conditions. In the larger context of railroad hazardous materials risk management, integrated accident prevention can be compared to other means of risk reduction measures, such as tank car safety design enhancement or operational changes.