This study investigated AJDO2 (arterio-jugular difference of oxygen content) in a large sample of severely head-injured patients to identify its pattern during the first days after injury and to describe the relationship of AJDO2 with acute neurological severity and with outcome 6 mo after trauma. In 229 comatose head-injured patients, we monitored intracranial pressure, cerebral perfusion pressure, and AJDO2. Outcome was defined 6 mo after injury. Jugular hemoglobin oxygen saturation (SjO2) averaged 68%. The mean AJDO2 was 4.24 vol% (SD, 1.3 vol%). There were 80 measurements (4.6%) with SjO2 <55% and 304 (17.6%) with saturation >75%. AJDO2 was higher than 8.7 vol% in 8 measurements (0.4%) and was lower than 3.9 vol% in 718 (42%) measurements. AJDO2 was higher during the first tests and decreased steadily over the next few days. Cases with a favorable outcome had a higher mean AJDO2 (4.3 vol%; SD, 0.3 vol%) than patients with severe disability or vegetative status (3.8 vol%; SD, 1.3 vol%) and patients who died (3.6 vol%; SD, 1 vol%). This difference was significant (P < 0.001). We conclude that low levels of AJDO2 are correlated with a poor prognosis, whereas normal or high levels of AJDO2 are predictive of better results.