Introduction: Needle stick injuries (NSIs) are a commonly encountered underreported occupational hazard faced by healthcare workers (HCWs). Aim: The aim of the study was to determine the causes of the NSI and reduce the NSI rate among all HCWs (doctors, nurses, technicians, general duty assistants/housekeeping staff) at a tertiary care hospital. Objectives: • To determine the rate of NSI among various categories of HCWs at a tertiary care hospital. • To study the causal factors and circumstances for NSIs. • To implement corrective actions and prevent these through improvement in training, usage of safety devices, and providing a safe environment. • To reduce the NSI rate per healthcare worker per year. • To reduce the NSI rate below the set benchmark of the hospital, i.e., one NSI per 1,000 in-patient days. Materials and methods: The causes for NSI were identified by collating the data from January 2016 to May 2017 and the Pareto analysis was used to find out the main factors leading to NSI. Continuous and scheduled training for nurses, doctors, phlebotomists, housekeeping staff, and general duty assistants (GDAs) on waste segregation [biomedical waste (BMW) management], handling of sharps/sharps container, and PPE usage was provided and the same was monitored by the infection control nurse and quality team during rounds. The NSI rates were presented to the clinical department heads and awareness was created among doctors to segregate the waste. Needles with safety device were made available for the nursing team for sample collection. The corrective action was implemented in the month of June 2017 and data for 3 months, i.e., June, July, and August 2017, were continuously monitored. Results: In the study, the main reasons for NSI were improper segregation of sharps in trained HCWs (38.46%), unavoidable accidents (30.77%), and improper handling of sharps (11.54%), followed by untrained person (6.41%), recapping of the needle (5.13%), and the safety device not being used at the time of sample collection (3.85%). After training and awareness of HCWs and promoting use of safety devices, data were collected and analyzed. Needle stick injury per HCW per year was reduced to 0.03 (June 2017–October 2017) from 0.05 (Jan 2016–May2017). Similarly, there was reduction in the NSI rate per thousand patient days to 0.63 (June 2017–Oct 2017) from 1.19 (Jan 2016–May2017). Conclusion: Needle stick injuries can be reduced by identifying the causative factors and implementing corrective measures like use of a safety device for sample collection, creating awareness about segregation of waste, and handling of sharps among all the HCWs including doctors.