Background/aim: Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specific antidote for its treatment, the aim of this study was to evaluate the effect of vitamin E in the treatment of acute AlP poisoning. Materials and methods: This was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition, the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma were measured. Results: There was no significant difference between the treatment and control groups with regard to demographic, clinical, or paraclinical data or Simplified Acute Physiology Score II (SAPSII) on admission. Systolic blood pressure significantly increased during the first 24 h in the treatment group (P < 0.05). The plasma MDA level significantly decreased in the treatment group (P < 0.05). Vitamin E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It significantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05). Conclusion: Vitamin E along with supportive treatment could have a therapeutic effect in acute AlP poisoning.