Abstract Background On January 31st, 2023, the province of British Columbia (BC), Canada, was granted a federal exemption allowing adults (aged 18 +) to possess up to 2.5 g of select illicit drugs. The exemption will be in place for three years (2023–2026), marking the first formal decriminalization of illicit drug policy reform in Canada. BC’s decriminalization initiative is premised on several goals. This project seeks to evaluate each of these goals and their individual and combined contributions to determine the overall success of this policy. Methods The following protocol paper provides a detailed outline of a five-year (2022-2027) national evaluation of BC’s decriminalization initiative, as well as the specific objectives, methodologies, and planned analyses for eight interrelated sub-studies that comprise the evaluation. These sub-studies fall under the following five topical areas of research: 1) people who use drugs (PWUD), 2) the police and the criminal justice system, 3) the general public, 4) the health services system, and 5) an economic analysis. Additional research activities may also be explored. Results The overall evaluation and specific sub-study designs were informed by intensive stakeholder engagement. The evaluation was developed in collaboration with an international expert committee who came together to undertake a nominal group technique to decide on the final evaluation design and corresponding logic model. The evaluation will also employ an advisory board and individual sub-study working groups comprised of experts and PWUD who will oversee the development and implementation of the overall evaluation as well as each sub-study. Discussion This evaluation will draw on implementation science research practices to evaluate and understand the full impacts of this novel drug policy experiment. Results will be widely disseminated through manuscripts, reports, presentations, and infographics, which will be adapted and tailored for specific audiences. The protocol identifies several anticipated challenges and limitations. This evaluation’s evidence-based findings will be poised to offer pivotal insights that can shape and refine the discourse on drug policy and will serve as a critical resource for understanding the multifaceted impacts of decriminalization.