Objectives: The purpose of this study was to analyze the factors which influence the willingness of injection drug users to participate in needle exchange and substitution therapy programs while both programs are still experimental. Methods: The multi-layer random sampling method was used in a cross-sectional survey conducted between February and March 2006, in which 1,206 samples were collected at the Yunlin and Chia-I Drug Abstention and Treatment Center of the Taichung Prison. Results: Of the injection drug users, 85.2% and 93% were willing to participate in needle exchange and substitution therapy programs, respectively. Belief in the program, identification card protection, peer pressure, and their sexual partner's encouragement were the factors which influenced willingness to participate in the needle exchange program, while belief in the program, the affordability of out-of-pocket volunteers, and their sexual partner's encouragement were the factors which determined willingness to participate in the substitution therapy program. Conclusions: Implementing peer education through the social network of high risk groups, propagating the benefits of these programs, eliminating the financial burden of substitution therapy for those out-of-pocket volunteers, and working together with law enforcement officials as a cohesive group may facilitate the overall implementation of the Harm Reduction Program.