Background: Organophosphorus (OP) pesticide poisoning is a major clinical and public health problem in India. Mortality rate remains high at 15%-30%. Aims: This prospective, observational study examines the relationship between pseudocholinesterase (PChE) activity and morbidity and mortality in OP poisoning. Setting and Design: OP poisoning cases admitted to a tertiary care center Intensive Care Unit (ICU) over 5 years from 2010 to 2014 were studied. Methods: Patients <16 years of age, those on steroids and those with neuromuscular weakness, were excluded from the study. Serum PChE level at admission was estimated and the severity of poisoning assessed accordingly. Primary outcome measures were ICU length of stay and ventilator-free days. Secondary outcome measures included vasopressor-free days, amount of atropine given, hospital length of stay, and ICU mortality. Results: There were 37 patients included in the study, aged between 24 and 44 years, of which 65% were male. They were divided into two groups according to PChE levels. Group A with PChE levels more than 1000 IU/L had twenty patients and Group B with levels <1000 IU/L had 17 patients. Group B had longer ICU length of stay (P < 0.001) and fewer ventilator-free days (P < 0.001). They also had a fewer vasopressor-free days and a longer stay in hospital. Conclusions: PChE level at presentation is a reliable indicator of the severity of OP poisoning and a predictor of the need for mechanical ventilation and the duration of stay in the ICU.