Patient-reported outcomes (PROs) are a distinctive method of evaluating patient response to health care or treatment. This systematic review aimed to analyse the impact of PROs in patients on direct oral anticoagulant (DOAC) treatment, prescribed for any indication (e.g. venous thromboembolism treatment or atrial fibrillation) using controlled trials (CT) and real-world observational studies (OS). A systematic search of articles was conducted according to PRISMA guidelines using databases, with the last update in November 2018. The Cochrane Collaboration tool for assessing bias in randomized CTs and the Newcastle-Ottawa Scale adapted for cross-sectional studies were used. Outcomes evaluated were related to health-related quality of life (HRQoL), satisfaction, adherence and compliance. Twenty-one original studies (6 CT, 15 OS) were included. HRQoL was assessed by 6 (1 CT, 5 OS) studies and reported that HRQoL scores were similar in patients on DOACs and warfarin. Patients prescribed DOACs presented higher HRQoL scores which were attributed to lack of intense monitoring required compared with warfarin but this was not statistically significant. The majority of studies (5 CT, 9 OS) investigated patient-reported satisfaction, indicating greater satisfaction with DOACs with significantly lower burden and increased benefit scores for patients on DOACs. Patient-reported expectations, compliance and adherence were similar for patients on DOACs and warfarin. Patients appear to prefer treatment with DOACs vs warfarin. This is shown by the higher quality of life, satisfaction and adherence described in the studies. However, heterogeneity in the analysed studies does not allow firm conclusions. © 2019 The British Pharmacological Society.