Objectives: Health-related quality of life (HRQL) is a key factor in making anticoagulant treatment decisions. The objective of this study was to assess the HRQL of patients with nonvalvular atrial fibrillation by treatment type: direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). Methods: We carried out a cross-sectional observational study with clinical practice data, gathering demographic and clinical variables. HRQL was measured using the 5-level 5dimension EuroQol questionnaire (EQ-5D-5L). Differences between the study groups in HRQL as measured by the EQ-5D-5L were analyzed using two-part multivariate regression models. First, using logistic regression, the adjusted probability, p(x), of having perfect health was estimated in each subgroup. Secondly, generalized linear models were used to estimate mean disutility values, w(x), in a population that does not have perfect health, i.e. utility less than 1 or 1-w(x). Results: We recruited 333 patients, of whom 126 were on DOACs and 207 on VKAs. A significant difference was observed in the EQ-5D-5L anxiety/depression dimension, with a higher percentage of patients classified in the 'no problems' category in the DOAC group. The same type of analysis did not identify significant differences in any of the other dimensions (mobility, self-care, usual activities or pain/discomfort). Discussion: In the multivariate model, utility was significantly higher in the DOAC group than in the VKA group, although the difference was small (0.0121). This difference is attributable to patients on DOACs having less anxiety/depression. Conclusion: Patients treated with DOACs report a slightly better quality of life than those treated with VKAs.