Purpose: The major complication of acute organophosphate (OP) poisoning is respiratory failure as a result of cholinergic toxicity. Many clinicians find it difficult to predict the optimal time to initiate mechanical ventilation (MV) weaning, and as a result have tended to provide a prolonged ventilator support period. The purpose of this study is to determine any clinical predictors based on patients characteristics and laboratory findings to assist in the optimal timing of mechanical ventilator weaning. Methods: We reviewed medical and intensive care records of 44 patients with acute OP poisoning who required mechanical ventilation admitted to medical intensive care unit between July 1998 and June 2007. Patient information regarding the poisoning, clinical data and demographic features, APACHE II score, laboratory data, and serial cholinesterase (chE) levels were collected. Base on the time period of MV, the patients were divided into two groups: early group (wean time < 7 days, n = 28) and delayed group (${geq}$ 7 days, n = 16). Patients were assessed for any clinical characteristics and predictors associated with the MV weaning period. Results: During the study period, 44 patients were enrolled in this study. We obtained the sensitivity and specificity values of predictors in the late weaning group. APACHE II score and a reciprocal convert of hypoxic index but specificity (83.8%) is only APACHE II score. Also, the chE concentration (rho = -0.517, p = 0.026) and APACHE II score (rho = 0.827, p < 0.001) correlated with a longer mechanical ventilation duration. Conclusion: In patients with acute OP poisoning who required mechanical ventilation, the APACHE II scoring system on a point scale of less than 17 and decrements in cholinesterase levels on 1-3 days were good predictors of delayed MV weaning.