We evaluated the bacteriological and clinical efficacy of the combination of ciprofloxacin/clindamycin in severe diabetic foot infections and we tried to elucidate the relationship between the vascular status of the lower limbs and the outcome of these infections. Initial empirical antibiotic therapy with ciprofloxacin (300 mg/12 hrs IV) and clindamycin (600 mg/8 hrs IV) was administered in 84 hospitalized diabetics with severe lower limb infections. This treatment was continued only in cases with primary clinical improvement. The major endpoints of treatment were: cure, improvement and failure. Evaluation of the vascular status of the lower extremities was performed by high resolution imaging coloured ultrasonography, US-Doppler and TcPO2 measurements. Polymicrobial flora was found in 83% of the cases with an average 2.8 species per specimen. Osteomyelitis was detected in 58 % of the patients. After five days of IV administration of ciprofloxacin and clindamycin the response rate was 95.2%. After three weeks of therapy the clinical outcome was: cure 54.8%, improvement 23.8%, and failure 21.4%. The long term follow up (mean duration 16 months) revealed complete healing of the skin lesions in 63 patients (75%). Unfavorable prognostic factors for these infections were: ankle systolic blood pressure <50 mmHg or toe systolic blood pressure < 30 mmHg and TcPO2 < 20 mmHg. The side effects of the combination of ciprofloxacin/clindamycin were mild and there were no cases of pseudomembranous enterocolitis. The combination of ciprofloxacin/clindamycin was found to provide an excellent empirical as well as definitive treatment of severe diabetic foot infections. The evaluation of the vascular status and the severity of ischaemia of the lower limbs has a strong predictive value in the outcome of these infections.