Abstract Objective Atrial fibrillation (AF) patients are prescribed oral-anticoagulant (OAC) therapy, often warfarin, to reduce stroke risk. We explored existing qualitative evidence about patients’ and health professionals’ experiences of OAC therapy. Methods Systematic searches of eight bibliographic databases were conducted. Quality was appraised using the Critical Appraisal Skills Programme tool and data from ten studies were synthesised qualitatively. Results Four third-order constructs, emerged from the final step in the analysis process: (1) diagnosing AF and the communication of information, (2) deciding on OAC therapy, (3) challenges revolving around patient issues, and (4) healthcare challenges. Synthesis uncovered perspectives that could not be achieved through individual studies. Conclusion Physicians’ and patients’ experiences present a dichotomy of opinion on decision-making, which requires further exploration and changes in practice. Outcomes of workload pressure on both health professionals and patients should be investigated. The need for on-going support and education to patients and physicians is critical to achieve best practice and treatment adherence. Practice implications Such research could encourage health professionals to understand and attend better to the needs and concerns of the patient. Additionally these findings can be used to inform researchers and healthcare providers in developing educational interventions with both patients and health professionals.