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S100B is a biochemical marker of head injury and optic nerve sheath diameter (ONSD) is a non-invasive bedside technique to detect intracranial pressure. We aim to demonstrate whether ONSD correlates with S100B protein in head injury patients with contusions and also whether the grade of contusion correlates with S100B protein. This is a prospective study done on head injury patients aged between 18 and 75 years having isolated contusions admitted within 24 h of injury. Patients were assessed neurologically with Glasgow Coma Scale (GCS) and cranial computed tomography study on admission. Ocular sonography was done for ONSD recording, and S100B protein venous samples were collected at 24 h, 48 h, and at discharge. The outcome was evaluated with Glasgow Outcome Scale (GOS) at discharge and 3 months. Out of 42 patients, the mean age was 46.2 years and 27 were males. There were 12 patients with mild, 25 with moderate, and 5 patients with severe head injury. The mean GCS at 24 h was 12.35, the mean ONSD at 24 h was 3.9 mm, and the mean S100B at 24 h was 0.214 µg/L. There was a statistically significant correlation noted between mean S100B and contusion grade. A moderate positive correlation was noted between ONSD and S100B at 48 h in mild and moderate head injury groups. Favorable outcome (GOS 4,5) at 3 months can be predicted by GCS, contusion grade, and S100B values. Better GCS (14 and 15), focal contusion grade, and S100B values (<0.5 µg/L) predict good outcome. Although ONSD and S100B give important information in different scenarios, S100B gives better predictive information in patients with traumatic cerebral contusions. [ABSTRACT FROM AUTHOR]