BACKGROUND AND PURPOSE: Weaning from a mechanical ventilator is a milestone in the recovery of seriously ill patients in Intensive care. Failure to wean and re-intubation adversely affects the outcome. The method of mechanical ventilation (MV) varies between different ICUs and so does the practice of weaning. Therefore, updated guidelines based on contemporary literature are designed to guide intensivists in modern ICUs. This is the first ISCCM Consensus Statement on weaning complied by a committee on weaning. The recommendations are intended to be used by all the members of the ICU (Intensivists, Registrars, Nurses, and Respiratory Therapists). METHODS: A Committee on weaning from MV, formed by the Indian Society of Critical Care Medicine (ISCCM) has formulated this statement on weaning from mechanical ventilators in intensive care units (ICUs) after a review of the literature. Literature was first circulated among expert committee members and allotted sections to each member. Sections of the statement written by sectional authors were peer-reviewed on multiple occasions through virtual meetings. After the final manuscript is accepted by all the committee members, it is submitted for peer review by central guideline committee of ISCCM. Once approved it has passed through review by the Editorial Board of IJCCM before it is published here as "ISCCM consensus statement on weaning from mechanical ventilator". As per the standard accepted for all its guidelines of ISCCM, we followed the modified grading of recommendations assessment, development and evaluation (GRADE) system to classify the quality of evidence and strength of recommendation. Cost-benefit, risk-benefit analysis, and feasibility of implementation in Indian ICUs are considered by the committee along with the strength of evidence. Type of ventilators and their modes, ICU staffing pattern, availability of critical care nurses, Respiratory therapists, and day vs night time staffing are aspects considered while recommending for or against any aspect of weaning. RESULT: This document makes recommendation on various aspects of weaning, namely, definition, timing, weaning criteria, method of weaning, diagnosis of failure to wean, defining difficult to wean, Use of NIV, HFOV as adjunct to weaning, role of tracheostomy in weaning, weaning in of long term ventilated patients, role of physiotherapy, mobilization in weaning, Role of nutrition in weaning, role of diaphragmatic ultrasound in weaning prediction etc. Out of 42 questions addressed; the committee provided 39 recommendations and refrained from 3 questions. Of these 39; 32 are based on evidence and 7 are based on expert opinion of the committee members. It provides 27 strong recommendations and 12 weak recommendations (suggestions). CONCLUSION: This guideline gives extensive review on weaning from mechanical ventilator and provides various recommendations on weaning from mechanical ventilator. Though all efforts are made to make is as updated as possible one needs to review any guideline periodically to keep it in line with upcoming concepts and standards. HOW TO CITE THIS ARTICLE: Clerk AM, Shah RJ, Kothari J, Sodhi K, Vadi S, Bhattacharya PK, . Position Statement of ISCCM Committee on Weaning from Mechanical Ventilator. Indian J Crit Care Med 2024;28(S2):S233-S248.