Phosphides poisoning is a commonly encountered poisoning in most developing countries and is emerging as a common self-poisoning agent. Over the past 20 years, biochemical markers of brain damage have been increasingly studied as potential tools for prognostic evaluation. S-100β protein is the β-subunit of a calcium binding protein present mainly in glial and Schwann cells. The current study was conducted to evaluate central nervous system affection and the prognostic value of S-100β protein for prediction of mortality after acute phosphides intoxication. Twenty nine patients admitted to Poison Control Unit (Emergency Hospital, Tanta University) suffering from acute phosphide poisoning in nine months period were included in this study. For all patients sociodemographic, clinical and toxicological data were explored. One milliliter venous blood was withdrawn for analysis of S-100β protein level. Primary outcome included mortality. Meanwhile, secondary outcomes included GCS, hypotension and length of hospital stay. There was statistical significant difference between survivor patients and non-survivor patients regarding blood pressure. Meanwhile, no statistical significant difference was noticed between survivors and non-survivors in either GCS, pulse or duration of hospital stay. Toxicological data of the participant patients revealed that (96.6%) of patients were in suicidal attempts by oral route. Zink phosphide was identified in (75.9%) of patients, while, aluminum phosphide was recognized in (24.1%) patients. Serum level of S-100β concentrations was significantly increased in phosphide intoxicated patients compared to the reference value for detection of injury to neural tissue (0.1 µg/L). There was significant negative statistical correlation between serum S-100β concentrations and GCS. Analysis of (ROC) curve of serum S-100β level as a predictor of mortality showed (AUC) = 0.956, P <0.0001* at a cut off value > 1.762 ug/l, serum S100β had a sensitivity of 100% and a specificity 95%. (PPV) was 95%, while (NPV) was 100%.