Introduction:Nurses have the highest rate of Needle Stick Injuries (NSIs) among health care workers. Objectives: 1. To determine the prevalence of NSIs in the past three months among nursing staffs and students of a Tertiary Care Hospital and the factors associated with it. 2. To assess the pre and post exposure prophylactic measures related to NSIs followed by them. Methodology: This cross-sectional study was conducted between May and June 2017 among 354 subjects including 218 staff nurses and 136 nursing students of a Tertiary Care Government Hospital in Chennai City. After the Institutional Ethics Committee approval, subjects were interviewed with a pre-designed semi structured questionnaire. Data was analysed using relevant descriptive and inferential statistics with trial version of SPSS.v. 25.0 Results: Prevalence of NSIs in the past three months was 29.7% (n=105). Majority 79 (58.1%) nursing students had experienced NSIs. Two handed recapping of syringes was significantly associated with NSIs (P = 0.001, OR = 4.363, 95% C.I = 2.033 -9.364). Around 40 (38.1%) of the NSIs had occurred most commonly at the In-patient wards. Majority 62 (59%) of them had never reported about their NSI while only 25 (23.8%) had reported regularly. Among those who got vaccinated with HBV vaccine (n=57) for pre-exposure prophylaxis,only 13(22%) had taken three doses of HBV. Conclusion: Two handed recapping of syringes, non-usage of gloves, lack of assistance and inattentiveness during procedures, especially among nursing students are the major associated factors for occurrence of NSIs.