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Introduction : Aluminum phosphide is a pesticide that is used in developing countries. Aluminum phosphide poisoning has a high mortality rate and there is no known antidote. This study aimed to evaluate the safety and efficacy of insulin-euglycemia therapy in the management of patients with acute aluminum phosphide poisoning. Methods : This trial was prospectively registered in the Pan African Clinical Trials Registry (PACTR202008534546951). A total of 108 patients were randomly allocated to two groups. The intervention group received insulin-euglycemia therapy in addition to standard treatment (norepinephrine and supportive care); the control group received standard treatment plus placebo. The main outcome measures were survival, blood pressure, and laboratory investigations. Results : The two groups had similar baseline parameters. Insulin-euglycemia therapy was associated with a significant reduction in mortality compared with that in the control group (64.8 percent and 96.3 percent, respectively; P value <0.001). Patients randomized to insulin-euglycemia also required lower doses of vasopressors (median was 7 mg versus 26 mg in control group; P value 0.006) and fewer patients needed intubation (61.1 percent versus 81.5 percent in the control group; P value 0.019). Insulin-euglycemia therapy significantly improved blood pressure (systolic, diastolic, and mean arterial pressure) (median at 6h post-admission was 80 mmHg, 55 mmHg and 65 mmHg compared with 20 mmHg, 10 mmHg and 13 mmHg in the control group respectively; P value <0.001) and bicarbonate and lactate concentrations. Conclusion : Insulin-euglycemia therapy appears to be a safe and effective treatment option for patients with aluminum phosphide poisoning. Vasopressor only therapy was associated with very poor outcomes in acute aluminum phosphide poisoning.