OBJECTIVES: Diabetic foot ulcers (DFU) cause substantial morbidity and are a risk factor for lower limb amputation. We assessed economic implications of offloading devices including fiberglass total contact casting (TCC), irremovable cast walker (iTCC) and removable cast walker (RCW) in the treatment of DFU patients in Ontario, Canada. METHODS: We developed a decision analytic model to determine the cost-effectiveness of TCC, iTCC and RCW compared with each other and with therapeutic shoes (TS) from the Ontario public payer perspective. Clinical model parameters (effectiveness and safety) of offloading devices were obtained from our systematic clinical evidence review. Costs of offloading devices and adverse events were taken from literature and expert opinions. Main outcomes of the model were incremental cost per healed ulcer, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). We conducted sensitivity analyses to explore the robustness of our findings. All costs were expressed in 2016 Canadian Dollars. RESULTS: RCW and TS were dominated by TCC and iTCC in both cost effectiveness and cost-utility analyses. In the cost-utility analysis, TCC was associated with 0.002 QALYs gained at an additional cost of $428 compared to iTCC over the 6-month time horizon. This translated into an ICER of $258,000 per QALY gained. The model was sensitive to time-to-healing using TCC, iTCC and healing probability of TCC and iTCC. Increased accessibility to an offloading device among DFU patients by 25% reduces the amputation cost by $16 million per year. CONCLUSIONS: RCW or TS was more expensive and less effective than TCC or iTCC in the treatment of DFU. iTCC is as effective as TCC in the treatment of patients with DFU and associated with fewer costs. iTCC should likely be the preferred option when acceptable to patients and clinicians. In situations where it cannot be used, TCC may be a reasonable alternative.