The outcome of acute osteomyelitis treated with sequential therapy consisting of a short course of parenteral antibiotics, followed by oral antibiotics, was studied. To be considered acute osteomyelitis, related symptoms must have been present for less than 2 weeks before diagnosis. Short-course parenteral antibiotics (therapy for 7 days or less) and then oral antibiotics were used to treat 29 patients (median age, 6.3 years). Pathogens were identified from blood cultures and bone aspirates. Staphylococcus aureus was isolated in 59%. Median duration of parenteral antibiotics and oral antibiotics was 4 days (range, 0-7 days) and 28 days (range, 14-42 days), respectively. Median duration of combined (parenteral and oral) therapy was 32 days (range, 20-49 days). No failures or complications were noted at the 6-month follow-up, which was available for 27 patients. Short-course parenteral antibiotic therapy followed by oral therapy appears to be effective for treatment of acute, uncomplicated osteomyelitis.