Background: Motivational interviewing (MI) may be an effective intervention to improve medication adherence in patients with schizophrenia. However, for this patient group, mixed results have been found in randomized controlled trials. Furthermore, the process of becoming (more) motivated for long-term medication adherence in patients with schizophrenia is largely unexplored. Method: We performed a qualitative multiple case study of MI-sessions to analyse the interaction process affecting motivation in patients with schizophrenia. Fourteen cases of patients with schizophrenia, who recently experienced a psychotic relapse after medication-nonadherence, were studied, comprising 66 audio-recorded MI-sessions. In the MI-sessions, the patients expressed their cognitions on medication. We used these cognitions to detect the different courses (or patterns) of the patients' ambivalence during the MI-intervention. We distinguished successful and unsuccessful cases, and used the cross-case-analysis to identify success factors to reach positive effects of MI. Results: Based on the expressed cognitions on medication, we found four different patterns of the patient process. We also found three success factors for the intervention, which were a trusting relationship between patient and therapist, the therapist's ability to adapt his MI-strategy to the patient's process, and relating patient values to long-term medication adherence. Conclusions: The success of an MI-intervention for medication adherence in patients with schizophrenia can be explained by well-defined success factors. Adherence may improve if therapists consider these factors during MI-sessions.