While leukocyte scintigraphy is accurate in detection of pedal osteomyelitis, there has been little data relating the technique to outcomes. We designed a trial to examine the prognostic value of sequential 99m Tc labeled leukocyte scans to establish the diagnosis of osteomyelitis and after three to four weeks of culture-guided antibiotic therapy. Twenty-three diabetic patients with proven pedal osteomyelitis (21/23) or persistent uptake (2/23) on the sequence of scans were studied. Five additional episodes of osteomyelitis developed in the group over the period of the study. Eleven patients demonstrated persistent uptake in the sequential scans. Nine progressed to amputation. The remaining two patients were biopsy-negative for infection, did not have cutaneous ulceration and were thought to have rapidly progressive arthropathy. Sequential leukocyte scintigraphy accurately predicts the need for amputation and can circumvent ineffective prolonged antibiotic therapy.