BACKGROUND Florid infection and osteomyelitis of the forefoot in patients with diabetic neuropathy often requires minor amputation, with risk of subsequent reulceration, reamputation, and patient dissatisfaction. We investigated use of an antibiotic-impregnated cement spacer (ACS) to release antibiotic locally to resolve residual infection and to fill the cavity created by debridement. METHODS We report 23 cases of osteomyelitis and associated severe infection of forefoot joints in 20 consecutive patients, age 60.3 +/- 13.4 years. Antibiotic-impregnated cement, extensive meticulous debridement, and ACS placement to fill the gap were employed in all cases. Deep cultures were taken routinely. Fixation with Kirschner wires was used as necessary. Mean followup was 21.2 +/- 10.2 months. A successful result was resolution of infection and wound healing to full skin closure without amputation. RESULTS Of 23 cases, 21 (91.3%) healed and two required toe amputation. ACS was left permanently in 10 patients, removed with arthrodesis in six, and removed without arthrodesis in five. One patient recovered but subsequently underwent transtibial amputation due to infection of a different site. CONCLUSIONS Severe infection associated with osteomyelitis of the foot in diabetic patients was successfully treated with extensive debridement and use of ACS, which filled the void created by debridement. Amputation was avoided in most patients. This procedure allowed extensive debridement through filling large voids with ACS, with prolonged antibiotic release.