The aim of the current analysis was to identify independent predictors of the overall clinical outcome of patients with atrial fibrillation (AF), including both stroke/thromboembolism and/or major bleeding. Given the overlap between stroke and bleeding risk factors, a composite risk-stratification score for stroke/thromboembolism or bleeding could potentially be developed.We used data from the vitamin K antagonist (VKA) arm (n = 2,293; 65% men; mean age 70 ± 9 years) of the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial, which was a multicenter, randomized, open-label noninferiority study that compared fixed-dose idraparinux with VKA in patients with AF. We defined two composite end points: end point 1 was the combination of stroke/thromboembolism or major bleeding; end point 2 was defined as the combination of stroke, systemic or venous embolism, myocardial infarction, cardiovascular death, or major bleeding.The independent predictors for composite end point 1 were age (P = .014), previous stroke/transient ischemic attack (P = .049), aspirin use (P = .002), and time in therapeutic range (P = .007). For composite end point 2, similar predictors were evident, plus left ventricular dysfunction (P = .011). Based on the regression models, two novel composite risk-prediction scores were developed and were validated externally in a “real-world” cohort of 441 outpatients with AF receiving anticoagulation treatment. Both composite scores 1 and 2 demonstrated numerically higher discriminatory performance (area under the curve [AUC], 0.728; 95% CI, 0.659-0.798 and AUC, 0.707; 95% CI, 0.655-0.758, for end points 1 and 2, respectively) and a positive net reclassification when compared with currently used risk models (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack], CHA2DS2VASc [cardiac failure or dysfunction, hypertension, age ≥ 75 years [doubled], diabetes, stroke (doubled)-vascular disease, age 65 to 74 years, and sex category (female)], and HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly]), but the differences were not statistically significant.We have developed and validated two novel composite scores for stroke/thromboembolism/bleeding that offer good discriminatory and predictive performance. However, these composite risk scores did not perform better than the easier and more practical “traditional” stroke and bleeding risk scores that are currently in use, which allow greater practicality and a more personalized balancing of risks.