Introduction: Organophosphorus poisoning (OP) continues to be a significant cause of morbidity and mortality with no definite predictors of outcome have been identified yet. The present study aimed to find parameters that could be used as predictors of major outcomes in acute OP poisoning. Patients and methods: This prospective, cohort study was carried out from the start of August 2019 to the end of July 2020 on cases with acute OP poisoning admitted to Tanta University Poison Control Center. All cases were subjected to history taking, clinical examination, assessment of poison severity score (PSS), laboratory investigations, electrocardiography, and assessment of outcome. Results and conclusion: One hundred and sixty-two cases were included. Their ages ranged from 18 to 74 years old. Males accounted for 55.6% of the cases. Most cases were intoxicated in suicidal attempts through ingestion of OP compounds. Statistically significant differences were found between cases that needed and didn't need intensive care unit (ICU) admission, mechanical ventilation (MV), and between survivors and non-survivors regarding GCS, O2 saturation, PSS, pH, bicarbonate level, and serum cholinesterase enzyme (SChE) level. Multivariate regression analyses revealed that the low GCS and the low O2 saturation were the independent risk factors for the need for ICU admission. Low O2 saturation was the sole risk factor for the need for MV. While the low O2 saturation and the low SChE level were the independent risk factors for mortality. Recommendations: It is recommended to assess the GCS, monitor the O2 saturation, and measure the level of SChE in all cases of OP poisoning at admission.