Background: One Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs. Methods: One hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed 'spray-on' skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed. Discussion: Outpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.