Objective: Improving adherence is a challenge and multiple barriers are likely to explain non-adherence. These barriers differ per patient and over course of the regimen. Hence, personalized interventions tailored to the specific barriers are needed. In a theoretical and evidence-based Tailored Multimedia Intervention, technology (online preparatory assessment, text messaging) was used as an add-on to a tailored counseling session (learned during a communication skills training), with the expectation of synergistic effects. Methods: A cluster randomized controlled trial was conducted in six hospitals, eight nurses and 160 chronic patients. Patient satisfaction with communication, beliefs about medication, self-efficacy and medication adherence were assessed at initiation of the treatment and after six months. Results: Intervention effects were found for patient satisfaction with nurses’ affective communication and self-efficacy at the initiation of treatment. The effect on self-efficacy remained after six months. Conclusion: By combining tailored counseling with technology, this intervention resulted in positive changes in important prerequisites of medication adherence. Practical implications: Technology can contribute significantly to health care providers’ ability to tailor information to the patients’ needs.