Background: Hospital-acquired infections (HAIs) are a threat to public health and addressing this issue will help to plan appropriate preventive strategies. Full-fledged active HAIs surveillance is the cornerstone in assessing the burden of HAIs. This study was planned to assess the burden of HAIs by implementing a hospital-wide active surveillance system in a large tertiary care teaching hospital in south India and compare findings with those of National Health Safety Network United States (NHSN US) and International Nosocomial Infection Control Consortium (INICC) India HAI rates. Materials and Methods: Active HAIs' surveillance was initiated in 18 Intensive Care Units (ICUs) from January 2015 to September 2016. All patients admitted in the ICUs were followed up by the infection control nurses, and surveillance was done for device-associated infections (DAIs). The cumulative rates of the DAIs and device utilization (DU) rates and surgical site infection (SSI) rates were determined for all the ICUs. These data were compared with corresponding NHSN and INICC India HAI rates. Results: Total number of patient days for the entire study period was 111294, pooled mean ventilator-associated pneumonia rate was 25.00/1000 ventilator days (NHSN US 2.0 and INICC India 9.4); Pooled mean central line-associated blood stream infection rate was 7.2/1000 central line days (NHSN US 1.1 and INICC India 5.1). The pooled mean ICU catheter-associated urinary tract infection rate was 6.1/1000 catheter days (2.1 NHSN US and 2.9 INICC India). The pooled mean SSI rate was found to be 3.5/100 surgeries. The DU rates had a significant positive agreement with the DAI rates. The DAI rates of most of the ICUs were found be to be higher than NHSN US and INICC India rates. Conclusion: There is an increasing need to implement an active surveillance system to detect and monitor the HAI rates which would be vital to implement infection control measures in a proactive manner rather than reactive.