Background: Cognitive Adaptation Training is a psychosocial intervention that focuses on reducing the negative effects of cognitive disorders, especially executive functions such as planning and targeted action. International research has shown that Cognitive Adaptation Training enhances multiple aspects of daily functioning in people with severe mental illnesses. Despite this evidence, implementation of the intervention into routine care remains a challenge. Objective: In this implementation research, a newly developed implementation program based on previous experience and scientific literature, is tested. The primary aim of this research is to assess the effectiveness of the implementation program. The secondary aim of this study is to evaluate the factors that impede or facilitate the implementation of Cognitive Adaptation Training. Methods: To test the effectiveness of the implementation program, a multicenter cluster randomized controlled trial was conducted comparing the implementation program to a single training program in four mental health institutions in The Netherlands. Focus groups, semistructured interviews, and questionnaires were used at multiple levels of service delivery (service user, professional, team, organization) to identify factors that may hamper or facilitate implementation. The RE-AIM framework was applied to measure the implementation effectiveness. Following this framework, the primary outcomes were Reach, Intervention Effectiveness, Adoption, Implementation, and Maintenance. These are assessed before, during, and after implementation. The research had a total duration of 14 months, with a follow-up measurement at 14 months. Data will be analyzed using multilevel modeling. Results: The study was funded in April 2018. Data collection occurred between November 2018 and January 2020. In total, 21 teams of 4 mental health institutions agreed to participate. Data analysis is ongoing and results are expected to be published in December 2020. Conclusions: This implementation research may provide important information about the implementation of psychosocial interventions in practice and may result in a program that is useful for Cognitive Adaptation Training, and possibly for psychosocial interventions in general. Trial Registration: The Netherlands Trial Register (NL7989); https://www.trialregister.nl/trial/7989. [JMIR Res Protoc 2020;9(8):e17412]