To establish a framework for implementing antimicrobial stewardship in Indian tertiary care hospitals, and identify challenges and enablers for implementation. Over 2018-2021 the Indian Council of Medical Research followed a systematic approach to establish a framework for implementation of antimicrobial stewardship in Indian hospitals. We selected 20 Indian tertiary care hospitals to study the feasibility of implementing a stewardship programme. Based on a questionnaire to lead physicians before and after the intervention, we assessed progress using a set of process and outcome indicators. In a qualitative survey we identified enablers and barriers to implementation of antimicrobial stewardship. We found an improvement in various antimicrobial stewardship implementation indicators in the hospitals after the intervention. All 20 hospitals conducted monthly point prevalence analysis of cultures compared with three hospitals before the intervention. The number of hospitals that initiated formulary restrictions increased from two to 12 hospitals and the number of hospitals that started practising prescription audit and feedback increased from six to 16 hospitals. Respondents in 15 hospitals expressed their willingness to expand the coverage of antimicrobial stewardship implementation to other wards and intensive care units. Six hospitals were willing to recruit the permanent staff needed for antimicrobial stewardship activities. Antimicrobial stewardship can be implemented in Indian tertiary hospitals with reasonable success, subject to institutional support, availability of trained manpower and willingness of hospitals to support antimicrobial stewardship-related educational and training activities.