OBJECTIVES: To determine the best oral anticoagulant(s) across four medical conditions: stroke prevention in atrial fibrillation (AF), primary prevention of venous thromboembolic disease (VTE), acute treatment of VTE, and secondary prevention of VTE; using network meta-analysis to compare novel oral anticoagulants (NOACs) with warfarin and/or low molecular weight heparin (LMWH). METHODS: We undertook four systematic reviews and network meta-analyses of randomised controlled trials. An extensive search and risk of bias assessment were followed by network meta-analyses within each condition, and additionally we performed combined meta-analyses across the four reviews for key safety outcomes. Through consultation between clinicians and methodologists, we needed to make various decisions about groupings of interventions and doses, and of different endpoints, for analysis. RESULTS: