Background. Tromethamine (THAM) has been demonstrated to reduce intracranial pressure (ICP). Early consideration for THAM may reduce the need for other measures for ICP control. Objective. To describe 4 cases of early THAM therapy for ICP control and highlight the potential to avoid TH and paralytics and achieve reduction in sedation and hypertonic/hyperosmotic agent requirements. Methods. We reviewed the charts of 4 patients treated with early THAM for ICP control. Results. We identified 2 patients with aneurysmal subarachnoid hemorrhage (SAH) and 2 with traumatic brain injury (TBI) receiving early THAM for ICP control. The mean time to initiation of THAM therapy was 1.8 days, with a mean duration of 5.3 days. In all patients, after 6 to 12 hours of THAM administration, ICP stability was achieved, with reduction in requirements for hypertonic saline and hyperosmotic agents. There was a relative reduction in mean hourly hypertonic saline requirements of 89.1%, 96.1%, 82.4%, and 97.0% for cases 1, 2, 3, and 4, respectively, comparing pre- to post-THAM administration. Mannitol, therapeutic hypothermia, and paralytics were avoided in all patients. Conclusions. Early administration of THAM for ICP control could potentially lead to the avoidance of other ICP directed therapies. Prospective studies of early THAM administration are warranted. ; Peer Reviewed