Background: Patients in the neurointensive care unit have high utilization of devices, thereby increased chance of getting device-associated infection (DAI). Central line-associated bloodstream infection (CLABSI) remains one of the most important DAI. Education remains an important part of the hospital infection control and improves the infection-control practices. Materials and methods: To evaluate the effectiveness of a quality initiative in reducing incidence of CLABSI, a prospective study (January 2017–December 2018) was done estimating CLABSI incidence before and after the intervention. Continuous teaching and training for hand hygiene practice and central-line catheter hub care were used as the tool for this study. Results: The quality improvement (QI) initiative achieved a 48% reduction in the CLABSI rate from the baseline rate of 8.7 to 4.5 per 1000 catheter days. The overall mortality showed a reduction from 1.5 to 0.05% during the post-intervention period. There was a significant improvement in compliance with the hand hygiene practice and catheter hub care in the post-intervention period. Discussion and conclusion: This study demonstrates adherence to hand hygiene and catheter hub care with continuous teaching, training, and supervision was highly effective in reducing the CLABSI rate. Clinical significance: Central line-associated bloodstream infection is one of the most important DAI causing significant morbidity and mortality in critically ill patient. Our findings support that continuous educational intervention of hand hygiene with and training on the catheter hub care are two most important preventive measures in the reduction of CLABSI incidence.