This prospective, randomized, multicenter trial compared the efficacy of two antibiotic regimens for treatment of foot infections in diabetic adults. Patients with infections requiring hospitalization were randomized to receive either intravenous ofloxacin followed by oral ofloxacin or intravenous ampicillin/sulbactam followed by oral amoxicillin/clavulanate (the aminopenicillin regimen) for 14-28 days. Patients with osteomyelitis were eligible for the study if the infected bone was to be removed. Of 108 patients enrolled in the study, 88 who were evaluable had various skin and soft-tissue infections, and 24% had osteomyelitis. For the ofloxacin and aminopenicillin regimens, the mean duration of intravenous therapy was 7.8 and 7.1 days, respectively, the mean duration of oral therapy was 13.2 and 12.0 days, respectively, the rate of eradication of pathogens was 78% and 88%, respectively, and the overall rate of clinical cure or improvement was 85% and 83%, respectively. Thus, about 3 weeks of therapy with either regimen was well tolerated and effective in treating these diabetic foot infections.