Outcome indicators of recurrence and amputation were used to evaluate risk factors and treatment choices in 454 patients with osteomyelitis who completed outpatient parenteral antimicrobial therapy (OPAT). Three hundred and fifteen (69.4%) were apparently cured at the time outcomes were measured and 139 (30.6%) had a recurrence. Of the recurrences, 56% occurred within 3 months, 78% within 6 months and 95% within 1 year. Both the initial pathogen and the choice of antibiotic had an effect on the risk of treatment failure. Osteomyelitis caused by Pseudomonas aeruginosa was associated with more than a two-fold increase in recurrence (P = 0.005) compared with infection caused by Staphylococcus aureus. There was a positive correlation between P. aeruginosa and amputation. With S. aureus infections, the risk of recurrence was more than twice as great with vancomycin therapy as opposed to treatment with beta-lactams (P = 0.03). Treatment with ceftriaxone was as effective as the penicillinase-resistant penicillins and cefazolin.