OBJECTIVES: To evaluate the effect of reinforcing an educational programme through telephone follow-up on health-related quality of life and anxiety and depression symptoms in individuals starting warfarin therapy. BACKGROUND: Educational interventions have improved quality of life in individuals using warfarin. Few studies have examined the addition of telephone follow-up to enhance educational interventions. DESIGN: Randomised controlled trial in outpatient setting. METHODS: Hospitalised adults starting warfarin therapy who agreed to participate received an educational programme about the warfarin treatment. At discharge, they were randomised to receive either five telephone follow-up calls (intervention) or no telephone calls (controls). Both groups were evaluated for health-related quality of life (using Duke Anticoagulation Satisfaction Scale) and symptoms of anxiety and depression (using Hospital Anxiety and Depression Scale) at three and six months post-discharge. Groups were compared at each time by independent-samples t test, and over time by repeated-measures analysis of variance, with time (three and six months), groups (intervention and control) and an interaction between time and group as factors. Level of significance was set at 0.05. The Consolidated Standards of Reporting Trials was used for reporting. RESULTS: Fifty-two individuals (26 per group) completed the study. There were no statistical differences between groups in health-related quality of life, anxiety and depression symptoms, at both times post-discharge. Participants who received follow-up telephone calls reported better positive psychological impact (a subscale of quality of life) than controls. CONCLUSIONS: Reinforcing an educational programme with telephone follow-ups did not have an overall effect on health-related quality of life of individuals using warfarin but promoted positive psychological impact. RELEVANCE TO CLINICAL PRACTICE: The low cost of reinforcing educational programmes with telephone calls and the improvement in positive psychological aspects indicate that this type of intervention is still a promising intervention that could be further investigated and improved.