OBJECTIVE The aim of the study was to evaluate the value of single-photon emission computed tomography/computed tomography (SPECT/CT) for therapy response assessment of jaw osteomyelitis. METHODS Thirty-four baseline and 74 follow-up SPECT/CT examinations for therapy response assessment were performed in 34 patients with jaw osteomyelitis. SPECT/CT and planar late-phase bone scintigraphy images were assessed at baseline and follow-up, according to the following criteria: tracer uptake grade (0 = no uptake, 1 = low uptake, 2 = moderate uptake and 3 = high uptake); and morphologic signs (osteolysis, sequestration, sclerosis, periosteal reaction and pathologic fracture). RESULTS At baseline, SPECT/CT showed marked (grade 2 or 3) uptake in 91% (31/34) of the patients, osteolysis in 85% (29/34), sclerosis in 71% (24/34), periosteal reaction in 44% (15/34) and a sequestrum in 24% (8/34). In 24 patients with clinically complete remission during or after at least 12 months' therapy, bone scintigraphy showed grade 0 or 1 uptake in 100% (24/24) and SPECT/CT in 91% (22/24) of the patients. Sclerosis with the disappearance of osteolysis, sequestration and periosteal reactions was the predominant morphologic finding in complete responders (68%; 16/24). In 10 patients with symptoms of exacerbation of the osteomyelitis, 80% (8/10) showed increasing uptake, 90% (9/10) sclerosis, 80% osteolysis (8/10) and 40% (4/10) osteolysis and periosteal reactions. CONCLUSIONS SPECT/CT is a valuable tool to accurately assess therapy response, disease exacerbation and complications of jaw osteomyelitis. Low-grade (grade 1) residual tracer uptake is common in patients with clinically complete remission and is suggestive of ongoing bone remodeling and healing.