INTRODUCTION: The relationship between anticoagulation efficacy and safety in obesity is complex and can vary between degrees of obesity and anticoagulant choice. Indeed, patients at extremes of body weight were under-represented in randomized trials. Additionally, the possibility of an 'obesity paradox' has been raised in atrial fibrillation, describing decreased thromboembolic risk in obese patients. AREAS COVERED: We explore the current literature on anticoagulation in obesity, specifically with regard to efficacy in atrial fibrillation, efficacy in venous thromboembolism, and bleeding risk. Pharmacodynamic and pharmacokinetic considerations are also discussed. EXPERT OPINION: As a class, direct oral anticoagulants are comparable to vitamin-K antagonists in preventing and treating thromboembolism in overweight and obese patients, whilst not increasing bleeding risk.