Introduction The aim of the Common factors, Responsiveness and Outcome in Psychotherapy (CROP) study is to identify client and psychologist characteristics and therapeutic processes associated with the outcome of psychotherapy delivered by psychologists employed in the Danish primary sector or fully self-employed. The study addresses two main questions. First, how are specific characteristics of clients and psychologists related to the outcome of therapy and do these characteristics moderate the outcome of different psychotherapeutic approaches? Second, to what extent do therapists adapt their approach to client characteristics and preferences and how does such responsiveness impact the process and outcome of therapy? Methods and analysis The study is a naturalistic prospective cohort study carried out in collaboration with psychologists in private practice in Denmark. Self-reported data are collected from the participating psychologists and their participating clients before, during (weekly and postsession) and after psychotherapy (at end of treatment and 3 months follow-up). The estimated target sample size is 573 clients. The data are analysed using multilevel modelling and structural equation modelling approaches to capture predictors and moderators of the effect and rate of change in psychotherapy as well as session-to-session changes during the therapy process. Ethics and dissemination The study has been approved by the IRB at the Department of Psychology, University of Copenhagen (IRB number: IP-IRB/01082018) and the Danish Data Protection Agency. All study data are fully anonymised and all clients have given informed consent to participation in the study. The study findings will be presented in articles in international, peer-reviewed journals as well as to psychotherapy practitioners and other professionals across Denmark. Trial registration number NCT05630560.