OBJECTIVES: The Drug Safety and Effectiveness Network (DSEN) in Canada was created in response for more evidence on ‘real world’ drug safety and effectiveness in the post-market phase. The goal of the Network Meta-Analysis (NMA) Collaborative was to establish within DSEN an innovative partnership of health methodologists with four distinct yet complementary areas of expertise relevant to network meta-analysis (biostatistics, safety/effectiveness systematic reviews, health economics, and knowledge translation) and closely linked with international experts and partner organizations such as ISPOR that are actively involved in health research. METHODS: A proposal was developed and submitted to the Canadian Institutes of Health Research (CIHR) for establishing a Collaborative for providing rapid response to specific queries by utilizing network meta-analysis and safety and effectiveness systematic reviews; providing a proactive platform for the development and application of innovative, sophisticated, leading edge analytical methods for NMA and safety and effectiveness systematic reviews; developing knowledge translation strategies that fill gaps in knowledge required by end-users to make evidence-based decisions about drug safety and effectiveness that are based on NMAs; establishing practical and interactive training and mentorship opportunities for trainees through international links with partners specializing in drug safety and effectiveness research. RESULTS: The proposal was peer-reviewed at CIHR for responding to safety and effectiveness using NMA, developing innovative NMA techniques, translating knowledge and building capacity.  The proposal was successful and funding was allocated.  The demonstration project awarded was evaluating new oral anti-coagulants compared to warfarin or low molecular weight heparin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. CONCLUSIONS: The infrastructure for the Collaborative will permit safety and effectiveness reviews involving NMA to be conducted and innovative methods developed.  The first review completed on new oral anti-coagulants incorporating NMA provided informative comparisons between the anticoagulants from both a therapeutic and economic perspective.