INTRODUCTION Anticholinesterase pesticides are widely used in agriculture and domestic settings throughout the world, and they are responsible for great morbidity and mortality. In Egypt and other developing countries, there is a pressing need for new affordable antidotes to treat anticholinesterase pesticide poisoning. Hence, this study was conducted to evaluate the safety and effectiveness of moderate doses of clonidine in the management of adult patients with acute anticholinesterase pesticide poisoning. METHODOLOGY This study was an open-label, phase II pilot clinical trial. Sixty patients with acute anticholinesterase pesticide poisoning gave consent to participate in the study. They were divided into 2 equal groups, with 30 patients in each group. Group I received clonidine plus the routine treatment, while group II received only the routine treatment. Patients were subjected to full history taking, and their vital and clinical data were recorded. Serum cholinesterase levels and routine laboratory investigations were measured. The different outcomes of the patients were assessed. RESULTS The baseline characteristics of both groups were similar. Thirteen (43.3%) patients developed significant hypotension during clonidine treatment. The clinical outcomes (including mortality, need for assisted ventilation, length of hospital stay, and total doses of atropine) showed no significant differences between the two groups. CONCLUSION The use of clonidine in acute anticholinesterase pesticide poisoning may be associated with a high incidence of hypotension requiring intervention. The clinical outcomes may not significantly improve in clonidine-treated patients.