Introduction Central venous access is one of the commonest procedures performed in acute care settings. The competence of staff nurses in caring for patients with Central Venous Catheters is an important determinant of quality patient outcomes and safety of patients in Intensive Care Units. Materials & Methods A pre-experimental study was done to assess the effectiveness of Central Line bundle Care upon Knowledge and Compliance regarding the Central Venous Catheter (CVC) among thirty Staff nurses from ICU’s of a selected Hospital were selected using Purposive sampling. The intervention was the education of nurses on Central Line bundle care by teaching and demonstration of Care. Tools included the self-administered structured questionnaire for knowledge regarding CVC and a Practice Checklist adapted from the JCIA based on bundle Care. Results Majority of the Nurses belonged to the age group of fewer than 25 years (76.66%, 70%) and had an experience less than 2 years (83.33%, 60%). Education of Nurses on bundle care was done using power point and demo for the nurses. The Comparison of Pretest knowledge scores (M=11.73, S.D=4.49) and Post-test knowledge scores (M=18.03, S.D=3.72) regarding the Care of CVC of nurses showed a significant improvement with t value of 5.82 at p<0.001.