Background Although psychotherapy is an effective treatment for depression, a large number of patients still do not receive care according to the protocols that are used in clinical trials. Instead, patients often receive a modified version of the original intervention. It is not clear how and when treatment protocols are used or modified in the Dutch specialized mental health care and whether these changes lead to suboptimal adherence to treatment protocols. Methods In the context of an ongoing multicenter trial that investigates whether twice-weekly sessions of protocolized interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) for depression lead to better treatment outcomes compared to once-weekly sessions, two focus groups using semi-structured interviews were organized. Aims were to increase insight in the adherence to and modifications of CBT and IPT protocols in the Dutch specialized mental health care for depression. Participants were fifteen therapists from seven mental health locations part of five mental health organizations. Verbatim transcripts were coded and analyzed using qualitative software. Results Three themes emerged: modification as the common practice, professional and patient factors influencing the adherence to protocols and organizational boundaries and flexibility. Treatment modification appeared to happen on a frequent basis, even in the context of a trial. Definitions of treatment modifications were multiple and varied from using intuition to flexible use of the same protocol. Therapist training and supervision, the years of work experience and individual characteristics of the therapist and the patient were mentioned to influence the adherence to protocols. Modifications of the therapists depended very much on the culture within the mental health locations, who differed in terms of the flexibility offered to therapists to choose and modify treatment protocols. Conclusions Not all treatment modifications were in line with existing evidence or guidelines. Regular ...