Objective: Restricted information exists to guide clinicians in selecting antibiotics for diabetic foot infections in Colombia. Because this serious complication causes substantial morbidity, mortality, and incurs major healthcare costs, we developed a decision tree model to determine, from the Ministry of Health's perspective, the cost-effectiveness in Colombia of the treatments recommended by the Infectious Diseases Society of America guidelines for mild diabetic foot infections Methods: A decision-tree model was developed using TreeAge® Pro-2007 and clinical experts. Success probabilities were derived from published randomized controlled trials. Drug costs were obtained from the Farmaprecios Guía de precios sugeridos al público, promedio del mercado para farmacias independientes. No 98 September-Octuber 2007. Thomson PLM. S.A. Bogotá D.C. and amputation and hospitalization costs from ISS 2001/2004 database, with values adjusted to 2007 using the Colombian inflation. One-way and two-way sensitivity analyses were performed to test the robustness of the decision tree model by varying the clinical success rates and costs of antibiotics. Probabilistic sensitivity analyses were also performed using Monte Carlo simulations Results: Clindamycin was cost-effective, dominating all other choices, and cephalexin had the next best profile. Expected success rates were 99.4% for clindamycin, 97.8% for cephalexin, 95.4% for amoxicillin-clavulanate, 95.2% for oxacillin and 95.0% for levofloxacin. The expected cost of clindamycin ($315,200 pesos (USD$157.28)) was lower than the next best alternative, cephalexin $366,560 pesos (USD$182.14); a cost difference of $51,360 pesos (USD$24.86) per patient treated. However, success rates were based on a single small trial for each drug (n<30 for each). In sensitivity analyses, the model/decision was sensitive to changes in efficacy rates and costs within plausible ranges for clindamycin and cephalexin. Conclusion: Clindamycin was cost-effective in treating mild diabetic foot infection but our model had several limitations/assumptions; consequently, the results should be interpreted cautiously. More clinical studies to evaluate oral antibiotics effectiveness are needed.