Objective To optimize the water extraction process for Taohong Siwu Decoction. Methods With paeoniflorin content and extract yield as indices, the orthogonal test was adopted to determine the optimal water amount, extraction time, and extraction times in the water extraction process for Taohong Siwu Decoction. Results In the optimal process, extraction was performed 3 times (1.5 h each) using water (12 times). Conclusion The optimized water extraction process is reasonable and feasible, which can provide a reference for the industrial production of Taohong Siwu Decoction.