OBJECTIVES: To investigate whether or not elimination of decision uncertainty related to the new anticoagulants would be cost-effective, by calculating the added value of conducting an RCT comparing the new oral anticoagulants (apixaban, dabigatran and rivaroxaban) relative to each other and relative to warfarin for stroke prevention in patients with atrial fibrillation. METHODS: We developed a decision analytic model, designed as a probabilistic Markov model containing 200 different probability distributions. The model included eight health states; atrial fibrillation (AF), heart failure, moderate stroke sequela, severe stroke sequela, atrial fibrillation with previous acute myocardial infarction (AMI), atrial fibrillation with previous stroke, major gastrointestinal bleeding and dead. Epidemiological input data was gathered from registries. Data on Quality of Life were based on published EQ-5D data and costs were based on national tariffs. Efficacy data included the three major randomised controlled trials comparing each of the new oral anticoagulants (apixaban, dabigatran and rivaroxaban) to warfarin. Current efficacy estimates indicate that the new anticoagulants are efficacious on some, but not all, outcomes compared to warfarin. However, no direct evidence comparing any of these new anticoagulants with each other is yet available.  RESULTS: Expected value of perfect information analysis on groups of parameters (EVPPI) for efficacy parameters was clearly much higher than EVPPI for other parameters (QALYs, costs and baseline risk epidemiological data). Population EVPPI for efficacy data was $ 1.3 billion in a population of 5 million, given an assumed threshold value of $ 100,000 per QALY gained. CONCLUSIONS: There is clearly an added value in conducting more research on the efficacy of new oral anticoagulants. Hence, new randomized controlled trial(s) comparing all of the new oral anticoagulants would probably decrease decision uncertainty considerably.