Background: Traumatic Brain Injury (TBI) is a global health problem. Preclinical trials in animals shows that early injection of progesterone after experimental TBI decreased brain edema, neuronal loss, and behavioral deficits. Erythropoietin (EPO) attenuates TBI due to its neuroprotective actions and its effect on erythropoiesis. Aim of Study: The aim of this study was to evaluate the effect of progesterone hormone versus erythropoietin on neurological outcome of patients with moderate traumatic brain injury. Material and Methods: The patients were randomly assigned to 3 equal groups (35 in each group). Group C (control): Standard care and treatment. Group P (progesterone): Standard care + progesterone 1mg/kg IM and then once/12 hours for 5 consecutive days. Group E (erythropoietin): Standard care + EPO IV 40,000IU within 6hr of the time of injury. The modified Marshall CT scan classification: Was obtained at admission and day 7. GCS: Daily evaluations over the initial 14-day period, adverse experiences, surgical procedures, intracranial complications and intake & output of fluids were recorded. Disability Rating Scale (DRS) were measured on admission and after 1 Mon., length of ICU & hospital stay and complications were measured. Results: There was statistically significant increase in GCS in group P compared to group C and E. There was statistically significant improvement in DRS in group P compared to group C and E on admission and after one month. There was statistically significant decrease in the length of ICU and hospital stay in group P compared to group C and E. Conclusion: Progesterone hormone and erythropoietin improved neurological outcome in moderate head injury patients in the form of improvement in GCS and DRS and decrease in the length of ICU and hospital stay with better outcome in progesterone in comparison with erythropoietin.