In this paper, the reaction characteristic of a novel reactive material, which introduced bismuth trioxide (Bi2O3) into traditional polytetrafluoroethylene/aluminum (PTFE/Al), is studied. The effect of Bi2O3 with different content and particle size on the reaction behaviors of PTFE/Al/Bi2O3 are investigated by drop-weight test and X-ray diffractometer (XRD), including impact sensitivity, energy release performance under a certain impact, and reaction mechanism. The experimental results show that the content of Bi2O3 increased from 0% to 35.616%, the characteristic drop height of impact sensitivity (H50) of PTFE/Al/Bi2O3 reactive materials decreased first and then increased, and the minimum H50 of all types of materials in the experiment is 0.74 times that of PTFE/Al, and the particle size of Bi2O3 affects the rate of H50 change with Bi2O3 content. Besides, with the increase of Bi2O3 content, both the reaction intensity and duration first increase and then decrease, and there is optimum content of Bi2O3 maximizing the reaction degree of the PTFE/Al/Bi2O3. Furthermore, a prediction model for the impact sensitivity of PTFE-based reactive material is developed. The main reaction products include AlF3, xBi2O3·Al2O3, and Bi.