The present study describes the protocol for the Ayahuasca Treatment Outcome Project (ATOP) with a special focus on the evaluation of addiction treatment services provided through Takiwasi Center, the first ATOP study site. The goal of the project is to assess treatment outcomes and understand the therapeutic mechanisms of an Ayahuascaassisted, integrative treatment model for addiction rehabilitation in the Peruvian Amazon. The proposed intervention protocol highlights the significance of treatment setting in the design, delivery, and efficacy of an addiction rehabilitation program that involves the potent psychedelic tea known as Ayahuasca. After describing the context of the study, we put forth details about our mixed-methods approach to data collection and analysis, with which we seek to gain an understanding of why, how, and for whom this specific ayahuasca-assisted treatment program is effective across a range of outcomes. The ATOP protocol employs qualitative research methods as a means to determine which aspects of the setting are meaningful to clients and practitioners, and how this may correlate with outcome measures. This paper delineates the core principles, methods, and measures of the overall ATOP umbrella, then discusses the role of ATOP in the context of the literature on long-term residential programs. To conclude, we discuss the strengths and limitations of the protocol and the intended future of the project.