BackgroundAtrial fibrillation (AF) and obesity affect over 60 and 650 million people, respectively.AimThis study aimed to explore clinician practices, beliefs, and attitudes towards the use of direct oral anticoagulants (DOACs) in obese adults (BMI ≥ 30 kg/m2) with AF.MethodSemi-structured interviews via video conference were conducted with multidisciplinary clinicians from across Australia, with expertise in DOAC use in adults with AF. Clinicians were invited to participate using purposive and snowball sampling techniques. Data were analysed in NVIVO using thematic analysis.ResultsFifteen clinicians including cardiologists (n = 5), hospital and academic pharmacists (n = 5), general practitioners (n = 2), a haematologist, a neurologist and a clinical pharmacologist participated. Interviews were on average 31 ± 9 min. Key themes identified were:Health system factors in decision-makingDisparities between rural and metropolitan geographic areas, availability of health services, and time limitations for in-patient decision-making, were described;Condition-related factors in decision-makingClinicians questioned the significance of obesity as part of decision-making due to the practical limitations of dose modification, and the rarity of the extremely obese cohort;Decision-making in the context of uncertaintyClinicians reported limited availability, reliability and awareness of primary evidence including limited guidance from clinical guidelines for DOAC use in obesity.ConclusionThis study highlights the complexity of decision-making for clinicians, due to the limited availability, reliability and awareness of evidence, the intrinsic complexity of the obese cohort and limited guidance from clinical guidelines. This highlights the urgent need for contemporary research to improve the quality of evidence to guide informed shared decision-making.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11096-023-01583-z.