OBJECTIVES: The RADIANT-4 trial demonstrated the clinical benefits of everolimus + best supportive care (BSC) versus BSC alone in patients with advanced progressive, non-functional neuroendocrine tumours (NET) of the GI or lung origin. We aimed to estimate the cost-effectiveness of everolimus plus BSC versus BSC alone in this population from a Canadian societal health care system perspective. METHODS: A partition survival analysis model with three health states estimated direct and indirect costs, quality adjusted life years (QALYs) and life years (LYs). Tunnel states were included for adverse events (AE) to derive AE specific costs. Clinical inputs for everolimus and BSC were based on the RADIANT-4 trial. Resource utilization frequency inputs were obtained from a Canadian survey of six physicians. Drug costs were obtained from IMSHealth^TMDeltaPA database; AE costs were obtained from Ontario Case Costing Initiative; other direct and indirect costs were obtained from official reimbursement lists from Ontario and other published sources. Utility inputs were derived from a mapping study of patients in the RADIANT-4 trial. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the parameter estimates. A 10-year time horizon was considered as a base case. RESULTS:  Everolimus was associated with an incremental QALYs of 0.616 or incremental LYs of 0.823 at an incremental cost of $CAN89,795, which translated to an ICER of $CAN145,670/QALY gained and $CAN109,166/LY gained. One way sensitivity analyses demonstrated that results were most sensitive to the extrapolation of hazard ratio for overall survival. Based on probabilistic sensitivity analysis, everolimus was 52.1%% cost-effective at a $CAN150,000 willingness to pay threshold. CONCLUSIONS:  Everolimus is a treatment option in patients with advanced, non-functional, progressive NET of GI or lung origin. With an ICER ranging from $CAN100K - $CAN150K, everolimus is a cost-effective treatment in patients with advanced (unresectable or metastatic), progressive, non-functional GI/lung NET patients in Canada.