Complex foot infections involving bone and soft tissue in patients with co-morbidities such as diabetes and peripheral arterial disease (PAD) are a cause of significant hospital admission. They are associated with substantial economic costs to health services worldwide. Historically, severe foot infection has been treated with surgical debridement and prolonged courses of systemic antibiotics. Prolonged systemic antibiotic use increases the risk of drug side effects, antimicrobial resistance and Clostridium difficile infection. The purpose of this study was to investigate whether surgical debridement and implantation of antibiotic loaded calcium sulfate is effective in the resolution of foot infection and wound healing. A retrospective cohort study of 137 consecutive cases of osteomyelitis (127) or significant soft tissue infection (10) over 62 months from 02/2013 to 04/2018 was conducted following local ethical approval. All cases of infection were treated with surgical debridement and local antibiotic-loaded calcium sulfate. The primary outcomes of infection resolution, time to healing and duration of postoperative antibiotics were measured. In 137 cases, 88.3% of infections resolved. Infection was eradicated in 22 patients without postoperative systemic antibiotics. About 82.5% of wounds healed, with an average healing time of 11.3 weeks. Healing time was significantly increased for the co-morbidities of diabetes and PAD (p =< .05) and for those requiring prolonged systemic postoperative antibiotics. Conservative surgical debridement and implantation of local antibiotic impregnated calcium sulfate is safe and effective in managing complex foot infections. We advocate early surgical intervention before deeper tissue involvement to help preserve lower limb structure and function.