Background Environmental cleaning is a fundamental principle in prevention and control of hospital acquired infections (HAIs) and reducing the microbial burden on the surfaces. Pathogens like vancomycin-Resistant Enterococci (VRE), Methicillin-Resistant Staphylococcus Aureus (MRSA), Multi Drug Resistant Organisms (MDROs), gram-negative bacilli, etc. can survive on inanimate surfaces from hours-days-months in a health-care settings. Routine and terminal environmental cleaning/disinfection plays a vital role in minimizing the outbreaks in hospitals which are recognized as a major contributor to morbidity and mortality of hospitalized patients. Methods Pre and post intervention, environment cultures were taken anonymously, and data was analyzed utilizing descriptive statistics. Causes and effects were studied, housekeeping staff practices were observed through direct observations, camera, and secret shoppers. Environmental cleaning guidelines and checklists were developed in the light of Center for Disease Control (CDC) and Prevention guidelines (2020), hands on practice and sessions were taken for housekeeping staff. Housekeeping supervisors were trained as train the trainers (TOT) to ensure compliance in all shifts round the clock 24/7. Plan-Do-Study-Act (PDSA) quality improvement methodology was followed together with process and outcome key performance indicators. Results Our MDRO rates decreased significantly i.e., from 4.7 to 2.8, the overall compliance rate of environmental cleaning and disinfection went up from 53% to 87%, compliance increased in 10 (71.4%) out of 14 components in checklist. Number of dusters and buckets increased substantially. Knowledge and practice of all housekeeping staff increased from 65% to 97%. All 380 (100%) housekeeping staff were trained and the concepts of high/low touch surfaces, sequence of cleaning from clean to dirty, dilution of disinfectant improved drastically. Zero MDROs were identified on pre and post cleaning of occupied and unoccupied bed's side rails, doorknob, mattress, remote control, IV pole, cardiac monitor etc. Conclusions Cleaning and disinfection of environmental surfaces is essential to prevent transmission of hospital acquired infections particularly MDROs. Environmental cleaning is a fundamental principle in prevention and control of hospital acquired infections (HAIs) and reducing the microbial burden on the surfaces. Pathogens like vancomycin-Resistant Enterococci (VRE), Methicillin-Resistant Staphylococcus Aureus (MRSA), Multi Drug Resistant Organisms (MDROs), gram-negative bacilli, etc. can survive on inanimate surfaces from hours-days-months in a health-care settings. Routine and terminal environmental cleaning/disinfection plays a vital role in minimizing the outbreaks in hospitals which are recognized as a major contributor to morbidity and mortality of hospitalized patients. Pre and post intervention, environment cultures were taken anonymously, and data was analyzed utilizing descriptive statistics. Causes and effects were studied, housekeeping staff practices were observed through direct observations, camera, and secret shoppers. Environmental cleaning guidelines and checklists were developed in the light of Center for Disease Control (CDC) and Prevention guidelines (2020), hands on practice and sessions were taken for housekeeping staff. Housekeeping supervisors were trained as train the trainers (TOT) to ensure compliance in all shifts round the clock 24/7. Plan-Do-Study-Act (PDSA) quality improvement methodology was followed together with process and outcome key performance indicators. Our MDRO rates decreased significantly i.e., from 4.7 to 2.8, the overall compliance rate of environmental cleaning and disinfection went up from 53% to 87%, compliance increased in 10 (71.4%) out of 14 components in checklist. Number of dusters and buckets increased substantially. Knowledge and practice of all housekeeping staff increased from 65% to 97%. All 380 (100%) housekeeping staff were trained and the concepts of high/low touch surfaces, sequence of cleaning from clean to dirty, dilution of disinfectant improved drastically. Zero MDROs were identified on pre and post cleaning of occupied and unoccupied bed's side rails, doorknob, mattress, remote control, IV pole, cardiac monitor etc. Cleaning and disinfection of environmental surfaces is essential to prevent transmission of hospital acquired infections particularly MDROs.